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Yun Y, An J, Kim HJ, Choi HK, Cho HY. Recent advances in functional lipid-based nanomedicines as drug carriers for organ-specific delivery. NANOSCALE 2025; 17:7617-7638. [PMID: 40026004 DOI: 10.1039/d4nr04778h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
Lipid-based nanoparticles have emerged as promising drug delivery systems for a wide range of therapeutic agents, including plasmids, mRNA, and proteins. However, these nanoparticles still encounter various challenges in drug delivery, including drug leakage, poor solubility, and inadequate target specificity. In this comprehensive review, we present an in-depth investigation of four distinct drug delivery methods: liposomes, lipid nanoparticle formulations, solid lipid nanoparticles, and nanoemulsions. Moreover, we explore recent advances in lipid-based nanomedicines (LBNs) for organ-specific delivery, employing ligand-functionalized particles that specifically target receptors in desired organs. Through this strategy, LBNs enable direct and efficient drug delivery to the intended organs, leading to superior DNA or mRNA expression outcomes compared to conventional approaches. Importantly, the development of novel ligands and their judicious combination holds promise for minimizing the side effects associated with nonspecific drug delivery. By leveraging the unique properties of lipid-based nanoparticles and optimizing their design, researchers can overcome the limitations associated with current drug delivery systems. In this review, we aim to provide valuable insights into the advancements, challenges, and future directions of lipid-based nanoparticles in the field of drug delivery, paving the way for enhanced therapeutic strategies with improved efficacy and reduced adverse effects.
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Affiliation(s)
- Yeochan Yun
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Jeongmin An
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Hyun Joong Kim
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
| | - Hye Kyu Choi
- Department of Chemistry and Chemical Biology, Rutgers University, the State University of New Jersey, 123 Bevier Road, Piscataway, New Jersey 08854, USA
| | - Hyeon-Yeol Cho
- Department of Bio & Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
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2
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Herpoldt K, López CL, Sappington I, Pham MN, Srinivasan S, Netland J, Montgomery KS, Roy D, Prossnitz AN, Ellis D, Wargacki AJ, Pepper M, Convertine AJ, Stayton PS, King NP. Macromolecular Cargo Encapsulation via In Vitro Assembly of Two-Component Protein Nanoparticles. Adv Healthc Mater 2024; 13:e2303910. [PMID: 38180445 PMCID: PMC11468305 DOI: 10.1002/adhm.202303910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/19/2023] [Indexed: 01/06/2024]
Abstract
Self-assembling protein nanoparticles are a promising class of materials for targeted drug delivery. Here, the use of a computationally designed, two-component, icosahedral protein nanoparticle is reported to encapsulate multiple macromolecular cargoes via simple and controlled self-assembly in vitro. Single-stranded RNA molecules between 200 and 2500 nucleotides in length are encapsulated and protected from enzymatic degradation for up to a month with length-dependent decay rates. Immunogenicity studies of nanoparticles packaging synthetic polymers carrying a small-molecule TLR7/8 agonist show that co-delivery of antigen and adjuvant results in a more than 20-fold increase in humoral immune responses while minimizing systemic cytokine secretion associated with free adjuvant. Coupled with the precise control over nanoparticle structure offered by computational design, robust and versatile encapsulation via in vitro assembly opens the door to a new generation of cargo-loaded protein nanoparticles that can combine the therapeutic effects of multiple drug classes.
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Affiliation(s)
- Karla‐Luise Herpoldt
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
- Present address:
2seventy BioSeattleWA98102USA
| | - Ciana L. López
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Isaac Sappington
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
| | - Minh N. Pham
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
| | - Selvi Srinivasan
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | - Jason Netland
- Department of ImmunologyUniversity of WashingtonSeattleWA98195USA
| | | | - Debashish Roy
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
| | | | - Daniel Ellis
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
| | - Adam J. Wargacki
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
| | - Marion Pepper
- Department of ImmunologyUniversity of WashingtonSeattleWA98195USA
| | - Anthony J. Convertine
- Department of BioengineeringUniversity of WashingtonSeattleWA98195USA
- Present address:
Department of Material Science and EngineeringMissouri University of Science and TechnologyRollaMO65409USA
| | | | - Neil P. King
- Department of BiochemistryUniversity of WashingtonSeattleWA98195USA
- Institute for Protein DesignUniversity of WashingtonSeattleWA98195USA
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3
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Alim E, Stone L, Sharma N, McMahon S, Allen Z, Aceto P, Victor P, Mitchell LF, Raulerson A, Schepke C, Grabowski J, Valera R, Kalia K, Fernandez M, Kouba K, Shannon M, Johnson V, Forestal C, Pongo I, Ospina S, Fontanez N, Rosenberg M, Levin M, Martinez D, Betancourt YP, Rhodes LV, Lee KJ. Single Live Cell Imaging of Multidrug Resistance Using Silver Ultrasmall Nanoparticles as Biosensing Probes in Triple-Negative Breast Cancer Cells. ACS APPLIED BIO MATERIALS 2023; 6:4672-4681. [PMID: 37844294 DOI: 10.1021/acsabm.3c00451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
Silver ultrasmall nanoparticles (Ag UNPs) (size < 5 nm) were used as biosensing probes to analyze the efflux kinetics contributing to multidrug resistance (MDR) in single live triple-negative breast cancer (TNBC) cells by using dark-field optical microscopy to follow their size-dependent localized surface plasmon resonance. TNBC cells lack expression of estrogen (ER-), progesterone (PR-), and human epidermal growth factor 2 (HER2-) receptors and are more likely to acquire resistance to anticancer drugs due to their ability to transport harmful substances outside the cell. The TNBC cells displayed greater nuclear and cytoplasmic efflux, resulting in less toxicity of Ag UNPs in a concentration-independent manner. In contrast, more Ag UNPs and an increase in cytotoxic effects were observed in the receptor-positive breast cancer cells that have receptors for ER+, PR+, and HER2+ and are known to better respond to anticancer therapies. Ag UNPs accumulated in receptor-positive breast cancer cells in a time-and concentration-dependent mode and caused decreased cellular growth, whereas the TNBC cells due to the efflux were able to continue to grow. The TNBC cells demonstrated a marked increase in survival due to their ability to have MDR determined by efflux of Ag UNPs outside the nucleus and the cytoplasm of the cells. Further evaluation of the nuclear efflux kinetics of TNBC cells with Ag UNPs as biosensing probes is critical to gain a better understanding of MDR and potential for enhancement of cancer drug delivery.
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Affiliation(s)
- Ece Alim
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Logan Stone
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Naina Sharma
- College of Medicine, University of Central Florida, Orlando, Florida 32827, United States
| | - Shane McMahon
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Zachary Allen
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Peter Aceto
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Paige Victor
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Luisa F Mitchell
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Arial Raulerson
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Connor Schepke
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Jamie Grabowski
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Rebecca Valera
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Karishma Kalia
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Mirtha Fernandez
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Kalli Kouba
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Matthew Shannon
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Victoria Johnson
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Christopher Forestal
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Immanuelle Pongo
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Sebastian Ospina
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Neysha Fontanez
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Madison Rosenberg
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Madison Levin
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Danna Martinez
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Yanel Pena Betancourt
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Lyndsay V Rhodes
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
| | - Kerry J Lee
- Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida 33965, United States
- College of Medicine, University of Central Florida, Orlando, Florida 32827, United States
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Dutt Y, Pandey RP, Dutt M, Gupta A, Vibhuti A, Vidic J, Raj VS, Chang CM, Priyadarshini A. Therapeutic applications of nanobiotechnology. J Nanobiotechnology 2023; 21:148. [PMID: 37149615 PMCID: PMC10163736 DOI: 10.1186/s12951-023-01909-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 04/24/2023] [Indexed: 05/08/2023] Open
Abstract
Nanobiotechnology, as a novel and more specialized branch of science, has provided a number of nanostructures such as nanoparticles, by utilizing the methods, techniques, and protocols of other branches of science. Due to the unique features and physiobiological characteristics, these nanostructures or nanocarriers have provided vast methods and therapeutic techniques, against microbial infections and cancers and for tissue regeneration, tissue engineering, and immunotherapies, and for gene therapies, through drug delivery systems. However, reduced carrying capacity, abrupt and non-targeted delivery, and solubility of therapeutic agents, can affect the therapeutic applications of these biotechnological products. In this article, we explored and discussed the prominent nanobiotechnological methods and products such as nanocarriers, highlighted the features and challenges associated with these products, and attempted to conclude if available nanostructures offer any scope of improvement or enhancement. We aimed to identify and emphasize the nanobiotechnological methods and products, with greater prospect and capacity for therapeutic improvements and enhancements. We found that novel nanocarriers and nanostructures, such as nanocomposites, micelles, hydrogels, microneedles, and artificial cells, can address the associated challenges and inherited drawbacks, with help of conjugations, sustained and stimuli-responsive release, ligand binding, and targeted delivery. We recommend that nanobiotechnology, despite having few challenges and drawbacks, offers immense opportunities that can be harnessed in delivering quality therapeutics with precision and prediction. We also recommend that, by exploring the branched domains more rigorously, bottlenecks and obstacles can also be addressed and resolved in return.
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Affiliation(s)
- Yogesh Dutt
- Department of Microbiology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
| | - Ramendra Pati Pandey
- Department of Microbiology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
- Department of Biotechnology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
| | - Mamta Dutt
- Mamta Dental Clinic, Opposite Sector 29, Main Badkhal Road, Faridabad, Haryana 121002 India
| | - Archana Gupta
- Department of Biotechnology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
| | - Arpana Vibhuti
- Department of Biotechnology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
| | - Jasmina Vidic
- Université Paris-Saclay, Micalis Institute, INRAE, AgroParisTech, 78350 Jouy-en-Josas, France
| | - V. Samuel Raj
- Department of Microbiology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
| | - Chung-Ming Chang
- Master & Ph.D Program in Biotechnology Industry, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302 Taiwan (ROC)
| | - Anjali Priyadarshini
- Department of Microbiology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
- Department of Biotechnology, SRM University, 39, Rajiv Gandhi Education City, Post Office P.S. Rai, Sonepat, Haryana 131029 India
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5
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IgG Fc Affinity Ligands and Their Applications in Antibody-Involved Drug Delivery: A Brief Review. Pharmaceutics 2023; 15:pharmaceutics15010187. [PMID: 36678816 PMCID: PMC9862274 DOI: 10.3390/pharmaceutics15010187] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/30/2022] [Accepted: 01/03/2023] [Indexed: 01/07/2023] Open
Abstract
Antibodies are not only an important class of biotherapeutic drugs, but also are targeting moieties for achieving active targeting drug delivery. Meanwhile, the rapidly increasing application of antibodies and Fc-fusion proteins has inspired the emerging development of downstream processing technologies. Thus, IgG Fc affinity ligands have come into being and have been widely exploited in antibody purification strategies. Given the high binding affinity and specificity to IgGs, binding stability in physiological medium conditions, and favorable toxicity and immunogenicity profiles, Fc affinity ligands are gradually applied to antibody delivery, non-covalent antibody-drug conjugates or antibody-mediated active-targeted drug delivery systems. In this review, we will briefly introduce IgG affinity ligands that are widely used at present and summarize their diverse applications in the field of antibody-involved drug delivery. The challenges and outlook of these systems are also discussed.
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6
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Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen. Nat Commun 2022; 13:5207. [PMID: 36064848 PMCID: PMC9441830 DOI: 10.1038/s41467-022-32910-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Accepted: 08/22/2022] [Indexed: 11/09/2022] Open
Abstract
Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.
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7
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Iijima M, Yamada Y, Nakano H, Nakayama T, Kuroda S. Bio-nanocapsules for oriented immobilization of DNA aptamers on aptasensors. Analyst 2022; 147:489-495. [PMID: 35023508 DOI: 10.1039/d1an02278d] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The oriented immobilization of sensing molecules (e.g., IgGs, receptors, lectins, and DNA aptamers) on sensor chips is particularly important for maximizing the potential of the sensing molecules, thereby enhancing the sensitivity and target-binding capacity of biosensors. We previously developed ∼30 nm bio-nanocapsules (ZZ-BNCs) consisting of the hepatitis B virus envelope L protein fused with the tandem form of protein A-derived IgG Fc-binding Z domain (ZZ-L protein). ZZ-BNC acts successfully as a scaffold, enhancing both the sensitivity and binding capacity of IgG, a Fc-fused receptor, and Fc-fused lectin to antigens, cytokines, and sugar chains through an oriented immobilization on a biosensor surface. To expand the versatility of ZZ-BNC, we modified ZZ-BNC by replacing the ZZ domain with a DNA-binding single-chain lambda Cro (scCro) domain, thereby developing scCro-BNC. The scCro-BNC was synthesized in yeast cells and homogeneously purified as ∼30 nm sized nanoparticles. In a quartz crystal microbalance, an scCro-BNC-coated sensor chip immobilized with thrombin-binding DNA aptamers showed an ∼5.5-fold higher thrombin-binding capacity and ∼6000-fold higher detection sensitivity than a sensor chip directly coated with DNA aptamers. In addition, the number of bound thrombin molecules per molecule of DNA aptamer increased by ∼7.8-fold with an scCro-BNC coating, consistent with the theoretical thrombin-binding capacity. Collectively, scCro-BNC was shown to perform as an ideal scaffold for maximizing the potential of the DNA aptamer by immobilizing it in an oriented manner. Facilitating a highly sensitive detection of various target molecules, these BNC-based scaffolds are expected to improve a wide range of biosensors while minimizing the number of sensing molecules required.
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Affiliation(s)
- Masumi Iijima
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.,Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya, Tokyo 156-8502, Japan
| | - Yuki Yamada
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.,Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
| | - Hideo Nakano
- Department of Applied Biosciences, Graduate School of Bioagricultural Science, Nagoya University, Chikusa, Nagoya, 464-8601, Japan
| | - Tsutomu Nakayama
- Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya, Tokyo 156-8502, Japan
| | - Shun'ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.,Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
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8
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Kim NH, Choi H, Shahzad ZM, Ki H, Lee J, Chae H, Kim YH. Supramolecular assembly of protein building blocks: from folding to function. NANO CONVERGENCE 2022; 9:4. [PMID: 35024976 PMCID: PMC8755899 DOI: 10.1186/s40580-021-00294-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/03/2021] [Indexed: 06/14/2023]
Abstract
Several phenomena occurring throughout the life of living things start and end with proteins. Various proteins form one complex structure to control detailed reactions. In contrast, one protein forms various structures and implements other biological phenomena depending on the situation. The basic principle that forms these hierarchical structures is protein self-assembly. A single building block is sufficient to create homogeneous structures with complex shapes, such as rings, filaments, or containers. These assemblies are widely used in biology as they enable multivalent binding, ultra-sensitive regulation, and compartmentalization. Moreover, with advances in the computational design of protein folding and protein-protein interfaces, considerable progress has recently been made in the de novo design of protein assemblies. Our review presents a description of the components of supramolecular protein assembly and their application in understanding biological phenomena to therapeutics.
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Affiliation(s)
- Nam Hyeong Kim
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Hojae Choi
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Zafar Muhammad Shahzad
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 16419, Republic of Korea
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Heesoo Ki
- Department of Nano Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Jaekyoung Lee
- Department of Nano Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Heeyeop Chae
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Yong Ho Kim
- SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 16419, Republic of Korea.
- Department of Nano Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
- Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea.
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9
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Hinuma S, Kuroda S. Binding of Hepatitis B Virus Pre-S1 Domain-Derived Synthetic Myristoylated Peptide to Scavenger Receptor Class B Type 1 with Differential Properties from Sodium Taurocholate Cotransporting Polypeptide. Viruses 2022; 14:v14010105. [PMID: 35062309 PMCID: PMC8780415 DOI: 10.3390/v14010105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/05/2022] [Accepted: 01/05/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: The myristoylated pre-S1 peptide (Myr47) synthesized to mimic pre-S1 domain (2-48) in large (L) surface protein of hepatitis B virus (HBV) prevents HBV infection to hepatocytes by binding to sodium taurocholate cotransporting polypeptide (NTCP). We previously demonstrated that yeast-derived nanoparticles containing L protein (bio-nanocapsules: BNCs) bind scavenger receptor class B type 1 (SR-B1). In this study, we examined the binding of Mry47 to SR-B1. (2) Methods: The binding and endocytosis of fluorescence-labeled Myr47 to SR-B1 (and its mutants)-green fluorescence protein (GFP) fusion proteins expressed in HEK293T cells were analyzed using flow cytometry and laser scanning microscopy (LSM). Various ligand-binding properties were compared between SR-B1-GFP and NTCP-GFP. Furthermore, the binding of biotinylated Myr47 to SR-B1-GFP expressed on HEK293T cells was analyzed via pull-down assays using a crosslinker and streptavidin-conjugated beads. (3) Conclusions: SR-B1 bound not only Myr47 but also its myristoylated analog and BNCs, but failed to bind a peptide without myristoylation. However, NTCP only bound Myr47 among the ligands tested. Studies using SR-B1 mutants suggested that both BNCs and Myr47 bind to similar sites of SR-B1. Crosslinking studies indicated that Myr47 binds preferentially SR-B1 multimer than monomer in both HEK293T and HepG2 cells.
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10
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Suffian IFBM, Al-Jamal KT. Bioengineering of virus-like particles as dynamic nanocarriers for in vivo delivery and targeting to solid tumours. Adv Drug Deliv Rev 2022; 180:114030. [PMID: 34736988 DOI: 10.1016/j.addr.2021.114030] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 09/16/2021] [Accepted: 10/27/2021] [Indexed: 12/12/2022]
Abstract
Virus-like particles (VLPs) are known as self-assembled, non-replicative and non-infectious protein particles, which imitate the formation and structure of original wild type viruses, however, lack the viral genome and/or their fragments. The capacity of VLPs to encompass small molecules like nucleic acids and others has made them as novel vessels of nanocarriers for drug delivery applications. In addition, VLPs surface have the capacity to achieve variation of the surface display via several modification strategies including genetic modification, chemical modification, and non-covalent modification. Among the VLPs nanocarriers, Hepatitis B virus core (HBc) particles have been the most encouraging candidate. HBc particles are hollow nanoparticles in the range of 30-34 nm in diameter and 7 nm thick envelopes, consisting of 180 or 240 copies of identical polypeptide monomer. They also employ a distinctive position among the VLPs carriers due to the high-level synthesis, which serves as a strong protective capsid shell and efficient self-assembly properties. This review highlights on the bioengineering of HBc particles as dynamic nanocarriers for in vivo delivery and specific targeting to solid tumours.
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Affiliation(s)
- Izzat F B M Suffian
- Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (Kuantan Campus), Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia.
| | - Khuloud T Al-Jamal
- Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
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11
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Hsu JC, Du Y, Sengupta A, Dong YC, Mossburg KJ, Bouché M, Maidment ADA, Weljie AM, Cormode DP. Effect of Nanoparticle Synthetic Conditions on Ligand Coating Integrity and Subsequent Nano-Biointeractions. ACS APPLIED MATERIALS & INTERFACES 2021; 13:58401-58410. [PMID: 34846845 PMCID: PMC8715381 DOI: 10.1021/acsami.1c18941] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Most current nanoparticle formulations have relatively low clearance efficiency, which may hamper their likelihood for clinical translation. Herein, we sought to compare the clearance and cellular distribution profiles between sub-5 nm, renally-excretable silver sulfide nanoparticles (Ag2S-NPs) synthesized via either a bulk, high temperature, or a microfluidic, room temperature approach. We found that the thermolysis approach led to significant ligand degradation, but the surface coating shell was unaffected by the microfluidic synthesis. We demonstrated that the clearance was improved for Ag2S-NPs with intact ligands, with less uptake in the liver. Moreover, differential distribution in hepatic cells was observed, where Ag2S-NPs with degraded coatings tend to accumulate in Kupffer cells and those with intact coatings are more frequently found in hepatocytes. Therefore, understanding the impact of synthetic processes on ligand integrity and subsequent nano-biointeractions will aid in designing nanoparticle platforms with enhanced clearance and desired distribution profiles.
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Affiliation(s)
- Jessica C Hsu
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Yu Du
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Arjun Sengupta
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Yuxi C Dong
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Katherine J Mossburg
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Mathilde Bouché
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
| | - Andrew D A Maidment
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
| | - Aalim M Weljie
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - David P Cormode
- Department of Radiology, University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, Pennsylvania 19104, United States
- Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
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12
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Sakai C, Hosokawa K, Watanabe T, Suzuki Y, Nakano T, Ueda K, Fujimuro M. Human hepatitis B virus-derived virus-like particle as a drug and DNA delivery carrier. Biochem Biophys Res Commun 2021; 581:103-109. [PMID: 34678685 DOI: 10.1016/j.bbrc.2021.10.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 10/04/2021] [Indexed: 01/05/2023]
Abstract
The controlled release of medications using nanoparticle-based drug delivery carriers is a promising method to increase the efficacy of pharmacotherapy and gene therapy. One critical issue that needs to be overcome with these drug delivery carriers is their target specificity. We focused on the cell tropism of a virus to solve this issue, i.e., we attempted to apply hepatitis B virus-like particle (HBV-VLP) as a novel hepatic cell-selective carrier for medication and DNA. To prepare HBV-VLP, 293T cells were transfected with expression plasmids carrying HBV envelope surface proteins, large envelope protein (L), and small envelope protein (S). After 72 h post-transfection, VLP-containing culture supernatants were harvested, and HBV-VLP was labeled with red fluorescent dye (DiI) and was purified by sucrose gradient ultracentrifugation. An anticancer drugs (geldanamycin or doxorubicin) and GFP-expressing plasmid DNA were incorporated into HBV-VLP, and medication- and plasmid DNA-loaded VLPs were prepared. We evaluated their delivery capabilities into hepatocytes, other organ-derived cells, and hepatocytes expressing sodium taurocholate cotransporting polypeptide (NTCP), which functions as the cellular receptor for HBV by binding to HBV L protein. HBV-VLP selectively delivered both anticancer drugs and plasmid DNA not into HepG2, Huh7, and other organ cells but into HepG2 cells expressing NTCP. In summary, we developed a novel delivery nanocarrier using HBV-VLP that could be used as a hepatitis selective drug- and DNA-carrier for cancer treatment and gene therapy.
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Affiliation(s)
- Chiho Sakai
- Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan
| | - Kohei Hosokawa
- Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan
| | - Tadashi Watanabe
- Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan
| | - Youichi Suzuki
- Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, 569-8686, Japan
| | - Takashi Nakano
- Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Osaka, 569-8686, Japan
| | - Keiji Ueda
- Division of Virology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
| | - Masahiro Fujimuro
- Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto, 607-8412, Japan.
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13
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Hamada H, Hamada H, Shimoda K, Mandai T, Ishihara K, Kiriake Y, Kuboki A. Synthesis of Ester-Linked Paclitaxel-Glycoside Conjugate as a Water-Soluble Paclitaxel Derivative—Maltoside Modification of Paclitaxel through Ester-Linker (Ester-Spacer). Nat Prod Commun 2021. [DOI: 10.1177/1934578x211038788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
To synthesize a water-soluble paclitaxel derivative, the anomers of diols of allyl 2,3,4-tri- O-benzyl-6- O-tritylglycoside (maltoside) were prepared, which can be separated by chromatographic procedure. One anomer was converted into α-glycosyloxyacetic acid (maltosyloxyacetic acid) by oxidative cleavage of the diol and subsequent oxidation. Ester-linked paclitaxel-glycoside conjugate, 7-glycolylpaclitaxel 2″- O-α-maltoside, was provided by condensation of 2′-TES paclitaxel with α-glycosyloxyacetic acid (maltosyloxyacetic acid) followed by deprotection of hydroxy groups.
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Affiliation(s)
| | - Hatsuyuki Hamada
- National Institute of Fitness and Sports in Kanoya, Kanoya, Japan
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14
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Artificial cells for the treatment of liver diseases. Acta Biomater 2021; 130:98-114. [PMID: 34126265 DOI: 10.1016/j.actbio.2021.06.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 05/06/2021] [Accepted: 06/03/2021] [Indexed: 12/13/2022]
Abstract
Liver diseases have become an increasing health burden and account for over 2 million deaths every year globally. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they also suffer limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic certain functions of a living cell have emerged as a new strategy to overcome some of the challenges that liver cell therapy faces at present. Artificial cells have demonstrated advantages in long-term storage, targeting capability, and tuneable features. This article provides an overview of the recent progress in developing artificial cells and their potential applications in liver disease treatment. First, the design of artificial cells and their biomimicking functions are summarized. Then, systems that mimic cell surface properties are introduced with two concepts highlighted: cell membrane-coated artificial cells and synthetic lipid-based artificial cells. Next, cell microencapsulation strategy is summarized and discussed. Finally, challenges and future perspectives of artificial cells are outlined. STATEMENT OF SIGNIFICANCE: Liver diseases have become an increasing health burden. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they have limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic certain functions of a living cell have emerged as a new strategy to overcome some of the challenges that liver cell therapy faces at present. This article provides an overview of the recent progress in developing artificial cells and their potential applications in liver disease treatment, including the design of artificial cells and their biomimicking functions, two systems that mimic cell surface properties (cell membrane-coated artificial cells and synthetic lipid-based artificial cells), and cell microencapsulation strategy. We also outline the challenges and future perspectives of artificial cells.
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15
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Hinuma S, Fujita K, Kuroda S. Binding of Nanoparticles Harboring Recombinant Large Surface Protein of Hepatitis B Virus to Scavenger Receptor Class B Type 1. Viruses 2021; 13:v13071334. [PMID: 34372540 PMCID: PMC8310236 DOI: 10.3390/v13071334] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 07/05/2021] [Indexed: 12/28/2022] Open
Abstract
(1) Background: As nanoparticles containing the hepatitis B virus (HBV) large (L) surface protein produced in yeast are expected to be useful as a carrier for targeting hepatocytes, they are also referred to as bio-nanocapsules (BNCs). However, a definitive cell membrane receptor for BNC binding has not yet been identified. (2) Methods: By utilizing fluorescence-labeled BNCs, we examined BNC binding to the scavenger receptor class B type 1 (SR-B1) expressed in HEK293T cells. (3) Results: Analyses employing SR-B1 siRNA and expression of SR-B1 fused with a green fluorescent protein (SR-B1-GFP) indicated that BNCs bind to SR-B1. As mutagenesis induced in the SR-B1 extracellular domain abrogates or attenuates BNC binding and endocytosis via SR-B1 in HEK293T cells, it was suggested that the ligand-binding site of SR-B1 is similar or close among high-density lipoprotein (HDL), silica, liposomes, and BNCs. On the other hand, L protein was suggested to attenuate an interaction between phospholipids and SR-B1. (4) Conclusions: SR-B1 can function as a receptor for binding and endocytosis of BNCs in HEK293T cells. Being expressed various types of cells, it is suggested that functions as a receptor for BNCs not only in HEK293T cells but also in other types of cells.
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Affiliation(s)
- Shuji Hinuma
- The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki 567-0047, Osaka, Japan
- Correspondence: (S.H.); (S.K.)
| | - Kazuyo Fujita
- Faculty of Human Life Science, Senri Kinran University, Fujisirodai 5-25-1, Suita 565-0873, Osaka, Japan;
| | - Shun’ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki 567-0047, Osaka, Japan
- Correspondence: (S.H.); (S.K.)
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16
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Fleischmann D, Goepferich A. General sites of nanoparticle biodistribution as a novel opportunity for nanomedicine. Eur J Pharm Biopharm 2021; 166:44-60. [PMID: 34087354 DOI: 10.1016/j.ejpb.2021.05.027] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/22/2021] [Accepted: 05/27/2021] [Indexed: 02/07/2023]
Abstract
The development of nanomedical devices has led to a considerable number of clinically applied nanotherapeutics. Yet, the overall poor translation of nanoparticular concepts into marketable systems has not met the initial expectations and led to increasing criticism in recent years. Most novel nano approaches thereby use highly refined formulations including a plethora of active targeting sequences, but ultimately fail to reach their target due to a generally high off-target deposition in organs such as the liver or kidney. In this context, we argue that initial nanoparticle (NP) development should not entirely become set on conventional formulation aspects. In contrast, we propose a change of focus towards a prior analysis of general sites of NP in vivo deposition and an assessment of how accumulation in these organs or tissues can be harnessed to develop therapies for site-related pathologies. We therefore give a comprehensive overview of existing nanotherapeutic targeting strategies for specific cell types within three of the usual suspects, i.e. the liver, kidney and the vascular system. We discuss the physiological surroundings and relevant pathologies of described tissues as well as the implications for NP-mediated drug delivery. Additionally, successful cell-selective NP concepts using active targeting strategies are assessed. By bringing together both (patho)physiological aspects and concepts for cell-selective NP formulations, we hope to show a novel opportunity for the development of more promising nanotherapeutic devices.
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Affiliation(s)
- Daniel Fleischmann
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany
| | - Achim Goepferich
- Department of Pharmaceutical Technology, University of Regensburg, Universitaetsstrasse 31, 93053 Regensburg, Germany.
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17
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Takagi K, Somiya M, Jung J, Iijima M, Kuroda S. Polymerized Albumin Receptor of Hepatitis B Virus for Evading the Reticuloendothelial System. Pharmaceuticals (Basel) 2021; 14:ph14050408. [PMID: 33923102 PMCID: PMC8145202 DOI: 10.3390/ph14050408] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 01/05/2023] Open
Abstract
Various strategies, such as optimization of surface chemistry, size, shape, and charge, have been undertaken to develop nanoparticles (NPs) as DDS (drug delivery system) nanocarriers for evading the reticuloendothelial system (RES) in vivo. We previously developed a hollow NP composed of hepatitis B virus (HBV) surface antigen L proteins and lipid bilayers, hereinafter referred to as bio-nanocapsule (BNC), as a nonviral DDS nanocarrier. Such a BNC harbors the HBV-derived human hepatic cell-specific infection mechanism, and intravenously injected BNCs by themselves were shown to avoid clearance by RES-rich organs and accumulate in target tissues. In this study, since the surface modification with albumins is known to prolong the circulation time of nanomedicines, we examined whether the polymerized albumin receptor (PAR) of BNCs contributes to RES evasion in mouse liver. Our results show that NPs conjugated with peptides possessing sufficient PAR activity were captured by Kupffer cells less efficiently in vitro and were able to circulate for a longer period of time in vivo. Comparing with polyethylene glycol, PAR peptides were shown to reduce the recognition by RES to equal content. Taken together, our results strongly suggest that the PAR domain of BNCs, as well as HBV, harbors an innate RES evasion mechanism. Therefore, the surface modification with PAR peptides could be an alternative strategy for improving the pharmacodynamics and pharmacokinetics of forthcoming nanomedicines.
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Affiliation(s)
- Kurumi Takagi
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; (K.T.); (M.I.)
| | - Masaharu Somiya
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan;
| | - Joohee Jung
- College of Pharmacy, Duksung Women’s University, Seoul 132-714, Korea;
| | - Masumi Iijima
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; (K.T.); (M.I.)
- Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Shun’ichi Kuroda
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; (K.T.); (M.I.)
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan;
- Correspondence:
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18
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Wang Y, Zhang Y, Yu Y, Ren L, Wang J, Cheng L, Jiang D, Guo X, Teng T, Luo X, Lv S, Wang X, Wang H, Shi X, Zhang H, Bi S. Preparation and preliminary evaluation of hepatitis B core antigen virus like nanoparticles loaded with indocyanine green. ANNALS OF TRANSLATIONAL MEDICINE 2021; 8:1661. [PMID: 33490173 PMCID: PMC7812214 DOI: 10.21037/atm-20-7478] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background In recent years, nanotechnology has attracted a plethora of attention due of its ability to effectively diagnose and treat various tumors. Virus-like particles (VLPs) have good biocompatibility, are safe and non-toxic, and have an internal hollow space, and as such they are often used as nano drug carriers. In recent years, it has become one of the hot spots in the field of biopharmaceutical engineering. Methods In this study, the tumor-targeting peptide RGD (Arg-Gly-Asp) was genetically inserted into the major immunodominant region (MIR) of the hepatitis B virus core protein (HBc). A series of characterization, including stability and optical properties, were evaluated. A visual diagnosis and analysis of the efficacy against tumor cells were conducted at the cell level and using a live animal model. Results This study demonstrated that the recombinant HBc-based VLPs could participate in self-assembly of monodispersed nanoparticles with well-defined morphology, and the near-infrared dye indocyanine green (ICG) could be packaged into the VLPs without any chemical modification. Moreover, the HBc-based VLPs could specifically target cancer cells via the interaction with overexpressed integrin αvβ3. The treatment with ICG-loaded HBc-based VLPs showed significant inhibition of 4T1 breast cancer cell growth (84.87% tumor growth inhibition). The in vivo imaging experiments demonstrated that the ICG-loaded HBc-based VLPs generated excellent fluorescence in tumor sites in 4T1 breast cancer bearing mice. This provided crucial information on tumor mass location, boundaries, and shape. Moreover, compared to free ICG, the nanosystem showed significantly longer blood circulation time and superior accuracy in targeting the tumor. Conclusions The ICG-loaded HBc-based VLPs prepared in this study were of good stability and biocompatibility. It showed strong tumor targeting specificity and tumor visualization. Thus, it is expected to provide a new experimental basis and theoretical support for the integration of VLPs in the clinical diagnosis and treatment of breast cancer.
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Affiliation(s)
- Yunlong Wang
- Henan Bioengineering Research Center, Zhengzhou, China.,Zhengzhou Technical College, Zhengzhou, China
| | - Yiqing Zhang
- Henan Bioengineering Research Center, Zhengzhou, China.,Zhengzhou Technical College, Zhengzhou, China
| | - Yinyin Yu
- Henan General Hospital, Zhengzhou, China
| | - Lei Ren
- Department of Biomaterials, Key Laboratory of Biomedical Engineering of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, China
| | - Jichuang Wang
- Henan Bioengineering Research Center, Zhengzhou, China
| | - Lei Cheng
- Henan Bioengineering Research Center, Zhengzhou, China
| | - Dandan Jiang
- Henan Bioengineering Research Center, Zhengzhou, China
| | - Xiangqian Guo
- School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Tieshan Teng
- School of Basic Medical Sciences, Henan University, Kaifeng, China
| | | | - Shuangyu Lv
- School of Basic Medical Sciences, Henan University, Kaifeng, China
| | | | - Huirui Wang
- Department of Radiation Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China
| | - Xinpeng Shi
- Department of Radiation Oncology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China
| | - Heng Zhang
- Henan General Hospital, Zhengzhou, China
| | - Shengli Bi
- Henan Bioengineering Research Center, Zhengzhou, China
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19
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Loo YS, Bose RJ, McCarthy JR, Mat Azmi ID, Madheswaran T. Biomimetic bacterial and viral-based nanovesicles for drug delivery, theranostics, and vaccine applications. Drug Discov Today 2020; 26:902-915. [PMID: 33383213 DOI: 10.1016/j.drudis.2020.12.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 11/16/2020] [Accepted: 12/21/2020] [Indexed: 01/04/2023]
Abstract
Smart nanocarriers obtained from bacteria and viruses offer excellent biomimetic properties which has led to significant research into the creation of advanced biomimetic materials. Their versatile biomimicry has application as biosensors, biomedical scaffolds, immobilization, diagnostics, and targeted or personalized treatments. The inherent natural traits of biomimetic and bioinspired bacteria- and virus-derived nanovesicles show potential for their use in clinical vaccines and novel therapeutic drug delivery systems. The past few decades have seen significant progress in the bioengineering of bacteria and viruses to manipulate and enhance their therapeutic benefits. From a pharmaceutical perspective, biomimetics enable the safe integration of naturally occurring bacteria and virus particles to achieve high, stable rates of cellular transfection/infection and prolonged circulation times. In addition, biomimetic technologies can overcome safety concerns associated with live-attenuated and inactivated whole bacteria or viruses. In this review, we provide an update on the utilization of bacterial and viral particles as drug delivery systems, theranostic carriers, and vaccine/immunomodulation modalities.
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Affiliation(s)
- Yan Shan Loo
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia
| | - Rajendran Jc Bose
- Masonic Medical Research Institute, 2150 Bleecker St, Utica, NY 13501, USA
| | - Jason R McCarthy
- Masonic Medical Research Institute, 2150 Bleecker St, Utica, NY 13501, USA
| | - Intan Diana Mat Azmi
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia.
| | - Thiagarajan Madheswaran
- Department of Pharmaceutical Technology, International Medical University, No. 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
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20
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Sun H, Chang L, Yan Y, Wang L. Hepatitis B virus pre-S region: Clinical implications and applications. Rev Med Virol 2020; 31. [PMID: 33314434 DOI: 10.1002/rmv.2201] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 11/22/2020] [Accepted: 11/29/2020] [Indexed: 12/12/2022]
Abstract
Hepatitis B virus (HBV) infection is a major threat to global public health, which can result in many acute and chronic liver diseases. HBV, a member of the family Hepadnaviridae, is a small enveloped DNA virus containing a circular genome of 3.2 kb. Located upstream of the S-open-reading frame of the HBV genome is the pre-S region, which is vital to the viral life cycle. The pre-S region has high variability and many mutations in the pre-S region are associated with several liver diseases, such as fulminant hepatitis (FH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). In addition, the pre-S region has been applied in the development of several pre-S-based materials and systems to prevent or treat HBV infection. In conclusion, the pre-S region plays an essential role in the occurrence, diagnosis, and treatment of HBV-related liver diseases, which may provide a novel perspective for the study of HBV infection and relevant diseases.
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Affiliation(s)
- Huizhen Sun
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, PR China
| | - Le Chang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China
| | - Ying Yan
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China
| | - Lunan Wang
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China
- Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, PR China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, PR China
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21
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Nishimura Y, Ezawa R, Morita K, Nakayama M, Ishii J, Sasaki R, Ogino C, Kondo A. In Vivo Evaluation of the Z HER2-BNC/LP Carrier Encapsulating an Anticancer Drug and a Radiosensitizer. ACS APPLIED BIO MATERIALS 2020; 3:7743-7751. [PMID: 35019514 DOI: 10.1021/acsabm.0c00951] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Radiosensitizing therapy for cancer treatment that enhances the effect of existing radiation therapy and enables noninvasive therapy has attracted attention. In this study, to achieve target cell-specific noninvasive cancer treatment using a ZHER2-bionanocapsule/liposome (BNC/LP), a carrier that binds to human epidermal growth factor receptor 2 (HER2), we evaluated the delivery of anticancer drugs and radiosensitizers and treatment effects in vitro and in vivo in mice. Target cell-specific cytotoxic activity and antitumor effects were confirmed following delivery of doxorubicin-encapsulated particles. In addition, cell damage due to radiosensitizing effects was confirmed in combination with X-ray irradiation following delivery of particles containing polyacrylic acid-modified titanium peroxide nanoparticles as a radiosensitizer. Furthermore, even when the particles were injected via the tail vein of mice, they accumulated in the tumor and exhibited an antitumor effect because of radiosensitization. Therefore, ZHER2-BNC/LP is expected to be a carrier that releases small-molecule drugs into the target cell cytoplasm and delivers a radiosensitizer such as inorganic nanoparticles, enabling combination therapy with X-rays to the target tumor.
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Affiliation(s)
- Yuya Nishimura
- Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
| | - Ryosuke Ezawa
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
| | - Kenta Morita
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
| | - Masao Nakayama
- Division of Radiation Oncology, Graduate School of Medicine, Kobe University, 7-5-2 Kusunokicho, Chuou-ku, Kobe 650-0017, Japan
| | - Jun Ishii
- Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
| | - Ryohei Sasaki
- Division of Radiation Oncology, Graduate School of Medicine, Kobe University, 7-5-2 Kusunokicho, Chuou-ku, Kobe 650-0017, Japan
| | - Chiaki Ogino
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
| | - Akihiko Kondo
- Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodaicho, Nada-ku, Kobe 657-8501, Japan
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22
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A Novel Hybrid Drug Delivery System for Treatment of Aortic Aneurysms. Int J Mol Sci 2020; 21:ijms21155538. [PMID: 32748844 PMCID: PMC7432022 DOI: 10.3390/ijms21155538] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/29/2020] [Accepted: 07/31/2020] [Indexed: 02/07/2023] Open
Abstract
Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair.
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23
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Thompson WS, Mondal G, Vanlith CJ, Kaiser RA, Lillegard JB. The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism. Expert Opin Orphan Drugs 2020; 8:245-256. [PMID: 33224636 PMCID: PMC7676758 DOI: 10.1080/21678707.2020.1791082] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Introduction Inborn errors of metabolism (IEMs) often result from single-gene mutations and collectively cause liver dysfunction in neonates leading to chronic liver and systemic disease. Current treatments for many IEMs are limited to maintenance therapies that may still require orthotropic liver transplantation. Gene therapies offer a potentially superior approach by correcting or replacing defective genes with functional isoforms; however, they face unique challenges from complexities presented by individual diseases and their diverse etiology, presentation, and pathophysiology. Furthermore, immune responses, off-target gene disruption, and tumorigenesis are major concerns that need to be addressed before clinical application of gene therapy. Areas covered The current treatments for IEMs are reviewed as well as the advances in, and barriers to, gene therapy for IEMs. Attention is then given to ex vivo and in vivo gene therapy approaches for hereditary tyrosinemia type 1 (HT1). Of all IEMs, HT1 is particularly amenable to gene therapy because of a selective growth advantage conferred to corrected cells, thereby lowering the initial transduction threshold for phenotypic relevance. Expert opinion It is proposed that not only is HT1 a safe indication for gene therapy, its unique characteristics position it to be an ideal IEM to develop for clinical investigation.
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Affiliation(s)
| | - Gourish Mondal
- Department of Surgery, Research Scientist, Mayo Clinic, Rochester, MN, USA
| | | | - Robert A Kaiser
- Department of Surgery, Research Scientist, Mayo Clinic, Rochester, MN, USA.,Midwest Fetal Care Center, Childrens Hospital of Minnesota, MN, USA
| | - Joseph B Lillegard
- Midwest Fetal Care Center, Childrens Hospital of Minnesota, MN, USA.,Assistant Professor of Surgery, Mayo Clinic, Rochester, MN, USA
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Böttger R, Pauli G, Chao PH, AL Fayez N, Hohenwarter L, Li SD. Lipid-based nanoparticle technologies for liver targeting. Adv Drug Deliv Rev 2020; 154-155:79-101. [PMID: 32574575 DOI: 10.1016/j.addr.2020.06.017] [Citation(s) in RCA: 136] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 05/26/2020] [Accepted: 06/16/2020] [Indexed: 12/18/2022]
Abstract
Liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma are global health problems accounting for approximately 800 million cases and over 2 million deaths per year worldwide. Major drawbacks of standard pharmacological therapies are the inability to deliver a sufficient concentration of a therapeutic agent to the diseased liver, and nonspecific drug delivery leading to undesirable systemic side effects. Additionally, depending on the specific liver disease, drug delivery to a subset of liver cells is required. In recent years, lipid nanoparticles have been developed to passively and actively target drugs to the liver. The success of this approach has been highlighted by the FDA-approval of the first liver-targeting lipid nanoparticle, ONPATTRO, in 2018 and many other promising candidate technologies are expected to follow. This review summarizes recent developments of various lipid-based liver-targeting technologies, namely solid-lipid nanoparticles, liposomes, niosomes and micelles, and discusses the challenges and future perspectives in this field.
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Construction of a Macrophage-Targeting Bio-nanocapsule-Based Nanocarrier. Methods Mol Biol 2019. [PMID: 31435929 DOI: 10.1007/978-1-4939-9798-5_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
Abstract
The construction protocol of bio-nanocapsule (BNC)-based nanocarriers, named GL-BNC and GL-virosome, for targeted drug delivery to macrophages is described here. First, genes encoding the Streptococcus sp. protein G-derived C2 domain (binds to IgG Fc) and Finegoldia magna protein L-derived B1 domain (binds to Igκ light chain) are prepared by PCR amplification. Subsequently, the genes encoding hepatic cell-specific binding domain of hepatitis B virus envelope L protein are replaced by these PCR products. The expression plasmid for this fused gene (encoding GL-fused L protein) can be used to transform Saccharomyces cerevisiae AH22R- cells. To obtain GL-BNC, the transformed yeast cells are disrupted with glass beads, treated with heat, and then subjected to IgG affinity column chromatography followed by size exclusion column chromatography. In addition, GL-BNCs can be fused with liposomes to form GL-virosome. The targeted delivery of GL-BNC and GL-virosome to macrophages can be confirmed by in vitro phagocytosis assays using the murine macrophage cell line RAW264.7.
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Yang G, Chen S, Zhang J. Bioinspired and Biomimetic Nanotherapies for the Treatment of Infectious Diseases. Front Pharmacol 2019; 10:751. [PMID: 31333467 PMCID: PMC6624236 DOI: 10.3389/fphar.2019.00751] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 06/11/2019] [Indexed: 12/21/2022] Open
Abstract
There are still great challenges for the effective treatment of infectious diseases, although considerable achievement has been made by using antiviral and antimicrobial agents varying from small-molecule drugs, peptides/proteins, to nucleic acids. The nanomedicine approach is emerging as a new strategy capable of overcoming disadvantages of molecular therapeutics and amplifying their anti-infective activities, by localized delivery to infection sites, reducing off-target effects, and/or attenuating resistance development. Nanotechnology, in combination with bioinspired and biomimetic approaches, affords additional functions to nanoparticles derived from synthetic materials. Herein, we aim to provide a state-of-the-art review on recent progress in biomimetic and bioengineered nanotherapies for the treatment of infectious disease. Different biomimetic nanoparticles, derived from viruses, bacteria, and mammalian cells, are first described, with respect to their construction and biophysicochemical properties. Then, the applications of diverse biomimetic nanoparticles in anti-infective therapy are introduced, either by their intrinsic activity or by loading and site-specifically delivering various molecular drugs. Bioinspired and biomimetic nanovaccines for prevention and/or therapy of infectious diseases are also highlighted. At the end, major translation issues and future directions of this field are discussed.
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Affiliation(s)
- Guoyu Yang
- Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China
- The First Clinical College, Chongqing Medical University, Chongqing, China
| | - Sheng Chen
- Department of Pediatrics, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Jianxiang Zhang
- Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China
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Liu Q, Somiya M, Iijima M, Tatematsu K, Kuroda S. A hepatitis B virus-derived human hepatic cell-specific heparin-binding peptide: identification and application to a drug delivery system. Biomater Sci 2019; 7:322-335. [PMID: 30474653 DOI: 10.1039/c8bm01134f] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Viruses are naturally evolved nanocarriers that can evade host immune systems, attach specifically to the surfaces of target cells, enter the cells through endocytosis, escape from endosomes efficiently, and then transfer their genomes to host cells. Hepatitis B virus (HBV) is a ∼42 nm enveloped DNA virus that can specifically infect human hepatic cells. To utilize the HBV-derived early infection machinery in synthetic nanocarriers, the human hepatic cell-binding site (i.e., the sodium taurocholate co-transporting polypeptide (NTCP)-binding site, with myristoylated pre-S1(2-47)) and the low pH-dependent fusogenic domain (pre-S1(9-24)) are indispensable for targeting and endosomal escape, respectively. However, cell-surface NTCP has recently been shown not to be involved in the initial attachment of HBV. In this study, we identified a novel heparin-binding site (pre-S1(30-42)) in the N-terminal half of the pre-S1 region, which presumably interacts with cell-surface heparan sulfate proteoglycan (HSPG) and plays a pivotal role in the initial attachment of HBV to human hepatic cells. The evolutionarily conserved amino acid residues Asp-31, Trp-32, and Asp-33 are indispensable for the heparin-binding activity. Liposomes (LPs) displaying the peptide were endocytosed by human hepatic cells in a cell-surface heparin-dependent manner and delivered doxorubicin to human hepatic cells more efficiently than myristoylated pre-S1(2-47)-displaying LPs. These results demonstrated that the pre-S1(30-42) peptide is the most promising HBV-derived targeting peptide for synthetic nanocarriers, and that this peptide exhibits high specificity for human hepatic cells and efficiently induces endocytosis.
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Affiliation(s)
- Qiushi Liu
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
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Iijima M, Araki K, Liu Q, Somiya M, Kuroda S. Oriented immobilization to nanoparticles enhanced the therapeutic efficacy of antibody drugs. Acta Biomater 2019; 86:373-380. [PMID: 30641288 DOI: 10.1016/j.actbio.2019.01.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 01/09/2019] [Accepted: 01/10/2019] [Indexed: 12/26/2022]
Abstract
Antibody drugs have been important therapeutic agents for treating various diseases, such as cancer, rheumatism, and hypercholesterolemia, for the last three decades. Despite showing excellent therapeutic efficacy with good safety in vivo, they require high doses. We have developed a ∼30-nm bio-nanocapsule (ZZ-BNC) consisting of hepatitis B virus envelope L protein fused with the tandem form of protein A-derived IgG Fc-binding Z domain (ZZ-L protein), for tethering antibodies in an oriented immobilization manner. In this study, antibody drugs were spontaneously conjugated to ZZ-BNC, which displayed the IgG Fv regions outwardly. The anti-human epidermal growth factor receptor IgG conjugated to ZZ-BNC (α-hEGFR-ZZ-BNC) was endocytosed by the human epidermoid carcinoma A431 cells, with increases in cellular uptake by ∼1.5 fold, compared that of α-hEGFR IgG alone. The amount of α-hEGFR IgG in the late endosomes and lysosomes was increased from 4% to 33% by the conjugation to ZZ-BNC. The in vitro cytotoxicity of α-hEGFR-ZZ-BNC was higher by ∼10-fold than that of α-hEGFR IgG alone. Furthermore, in vivo tumor growth was significantly reduced by α-hEGFR-ZZ-BNC than by α-hEGFR IgG alone. Taken together, since endosomal EGFR, not cell surface EGFR, played a pivotal role in the EGFR-mediated signaling cascade, ZZ-BNC increased α-hEGFR IgG avidity by efficiently repressing the activation of hEGFR not only on the cell surface, but presumably also in the endosomes. These results strongly suggested that ZZ-BNC is a promising nano-scaffold for enhancing the therapeutic efficacy and reducing the dose of antibody drugs. STATEMENT OF SIGNIFICANCE: Antibody drugs are widely used for treating severe diseases, such as cancer, rheumatism, and hypercholesterolemia. These drugs are composed of naturally occurring biomaterials with low immunogenicity and toxicity, as well as long in vivo serum half-life. To achieve sufficient therapeutic efficacy, the dose of antibody drugs are unavoidably higher than those of conventional drugs. The present study shows an innovative way to reduce the dose of antibody drugs by using a nanocarrier-conjugated antibody. Oriented immobilization of the antibody enhanced its avidity, endocytosis efficiency, and therapeutic efficacy.
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Affiliation(s)
- Masumi Iijima
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Kyoko Araki
- Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan
| | - Quishi Liu
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan
| | - Masaharu Somiya
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Shun'ichi Kuroda
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan.
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Abstract
The objective of this article is to propose a re-visiting of the paradigms of nano-carriers based drug routeing from an industrial viewpoint. The accumulation of drugs in specific body compartments after intravenous administration and the improvement of the oral bioavailability of peptides were taken as examples to propose an update of the translational framework preceding industrialisation. In addition to the recent advances on the biopharmacy of nano-carriers, the evolution of adjacent disciplines such as the biology of diseases, the chemistry of polymers, lipids and conjugates, the physico-chemistry of colloids and the assembling of materials at the nanoscale (referred to as microfluidics) are taken into account to consider new avenues in the applications of drug nano-carriers. The deeper integration of the properties of the drug and of the nano-carrier, in the specific context of the disease, advocates for product oriented programmes. At the same time, the advent of powerful collaborative digital tools makes possible the extension of the expertise spectrum. In this open-innovation framework, the Technology Readiness Levels (TRLs) of nano-carriers are proposed as a roadmap for the translational process from the Research stage to the Proof-of-Concept in human.
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Affiliation(s)
- Harivardhan Reddy Lakkireddy
- a Pre-Development Sciences, Pharmaceutical Development Platform , Sanofi Research & Development , Paris , France
| | - Didier V Bazile
- b Integrated CMC External Innovation , Sanofi Research & Development , Paris , France
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31
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Matsuo H, Somiya M, Iijima M, Arakawa T, Kuroda S. CD11c-specific bio-nanocapsule enhances vaccine immunogenicity by targeting immune cells. J Nanobiotechnology 2018; 16:59. [PMID: 30077180 PMCID: PMC6076409 DOI: 10.1186/s12951-018-0386-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Accepted: 07/28/2018] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Various nanocarriers have been used to deliver subunit vaccines specifically to dendritic cells (DCs) for the improvement of immunogenicity. However, due to their insufficient DC priming ability, these vaccines could not elicit effective innate immunity. We have recently developed a DC-targeting bio-nanocapsule (BNC) by displaying anti-CD11c IgGs via protein A-derived IgG Fc-binding Z domain on the hepatitis B virus envelope L protein particles (α-DC-ZZ-BNC). RESULTS After the chemical modification with antigens (Ags), the α-DC-ZZ-BNC-Ag complex could deliver Ags to DCs efficiently, leading to effective DC maturation and efficient endosomal escape of Ags, followed by Ag-specific T cell responses and IgG productions. Moreover, the α-DC-ZZ-BNC modified with Japanese encephalitis virus (JEV) envelope-derived D3 Ags could confer protection against 50-fold lethal dose of JEV injection on mice. CONCLUSION The α-DC-ZZ-BNC-Ag platform was shown to induce humoral and cellular immunities effectively without any adjuvant.
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Affiliation(s)
- Hidenori Matsuo
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601 Japan
| | - Masaharu Somiya
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047 Japan
| | - Masumi Iijima
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601 Japan
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047 Japan
- Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, 156-8502 Japan
| | - Takeshi Arakawa
- COMB, Tropical Biosphere Research Center, University of the Ryukyus, Nishihara, Okinawa 903-0213 Japan
- Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215 Japan
| | - Shun’ichi Kuroda
- Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601 Japan
- Department of Biomolecular Science and Reaction, The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047 Japan
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Hamada H, Okada S, Masuoka N, Fujitaka Y, Shimoda K, Doi S, Mikuni K. Synthesis of Ester-linked Taxol-oligosaccharide Conjugate and Its Drug Delivery System Using Bio-nanocapsules and Hybrid-bio-nanocapsules. Nat Prod Commun 2018. [DOI: 10.1177/1934578x1801300803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Synthesis of ester-linked oligosaccharide conjugate of taxol, i.e., 7-glycolyltaxol 2″- O-α-maltotrioside, was investigated by enzymatic procedure. The starting material, 7-glycolyltaxol 2″- O-α-D-glucoside, was glycosylated by cyclodextrin glucanotransferase to 7-glycolyltaxol 2″- O-α-maltooligosides [α-maltooligosaccharides; α-Glc-1→(4-α-Glc-1→)n-14-α-glucosides (n = 1–4)]. The enzymatic hydrolysis of 7-glycolyltaxol 2″- O-α-maltooligosides gave 7-glycolyltaxol 2″- O-α-maltotrioside. Both bio-nanocapsules and hybrid-bio-nanocapsules containing 7-glycolyltaxol 2″- O-α-maltotrioside exhibited high in vitro anti-tumor activities.
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Affiliation(s)
- Hiroki Hamada
- Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
| | - Shouta Okada
- Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
| | - Noriyoshi Masuoka
- Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
| | - Yuya Fujitaka
- Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
| | - Kei Shimoda
- Department of Biomedical chemistry, Faculty of Medicine, Oita University, 1-1 Hasama-machi, Oita 879-5593, Japan
| | - Shouta Doi
- Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
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Li H, Tatematsu K, Somiya M, Iijima M, Kuroda S. Development of a macrophage-targeting and phagocytosis-inducing bio-nanocapsule-based nanocarrier for drug delivery. Acta Biomater 2018; 73:412-423. [PMID: 29673839 DOI: 10.1016/j.actbio.2018.04.023] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 03/28/2018] [Accepted: 04/11/2018] [Indexed: 12/11/2022]
Abstract
Macrophage hyperfunction or dysfunction is tightly associated with various diseases, such as osteoporosis, inflammatory disorder, and cancers. However, nearly all conventional drug delivery system (DDS) nanocarriers utilize endocytosis for entering target cells; thus, the development of macrophage-targeting and phagocytosis-inducing DDS nanocarriers for treating these diseases is required. In this study, we developed a hepatitis B virus (HBV) envelope L particle (i.e., bio-nanocapsule (BNC)) outwardly displaying a tandem form of protein G-derived IgG Fc-binding domain and protein L-derived IgG Fab-binding domain (GL-BNC). When conjugated with the macrophage-targeting ligand, mouse IgG2a (mIgG2a), the GL-BNC itself, and the liposome-fused GL-BNC (i.e., GL-virosome) spontaneously initiated aggregation by bridging between the Fc-binding domain and Fab-binding domain with mIgG2a. The aggregates were efficiently taken up by macrophages, whereas this was inhibited by latrunculin B, a phagocytosis-specific inhibitor. The mIgG2a-GL-virosome containing doxorubicin exhibited higher cytotoxicity toward macrophages than conventional liposomes and other BNC-based virosomes. Thus, GL-BNCs and GL-virosomes may constitute promising macrophage-targeting and phagocytosis-inducing DDS nanocarriers. STATEMENT OF SIGNIFICANCE We have developed a novel macrophage-targeting and phagocytosis-inducing bio-nanocapsule (BNC)-based nanocarrier named GL-BNC, which comprises a hepatitis B virus envelope L particle outwardly displaying protein G-derived IgG Fc- and protein L-derived IgG Fab-binding domains in tandem. The GL-BNC alone or liposome-fused form (GL-virosomes) could spontaneously aggregate when conjugated with macrophage-targeting IgGs, inducing phagocytosis by the interaction between IgG Fc of aggregates and FcγR on phagocytes. Thereby these aggregates were efficiently taken up by macrophages. GL-virosomes containing doxorubicin exhibited higher cytotoxicity towards macrophages than ZZ-virosomes and liposomes. Our results suggested that GL-BNCs and GL-virosomes would serve as promising drug delivery system nanocarriers for targeting delivery to macrophages.
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Affiliation(s)
- Hao Li
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan
| | - Kenji Tatematsu
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan
| | - Masaharu Somiya
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan
| | - Masumi Iijima
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan
| | - Shun'ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan.
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Zhang Q, Shan W, Ai C, Chen Z, Zhou T, Lv X, Zhou X, Ye S, Ren L, Wang X. Construction of Multifunctional Fe 3O 4-MTX@HBc Nanoparticles for MR Imaging and Photothermal Therapy/Chemotherapy. Nanotheranostics 2018; 2:87-95. [PMID: 29291165 PMCID: PMC5743840 DOI: 10.7150/ntno.21942] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2017] [Accepted: 11/10/2017] [Indexed: 01/23/2023] Open
Abstract
To accomplish effective cancer imaging and integrated therapy, the multifunctional nanotheranostic Fe3O4-MTX@HBc core-shell nanoparticles (NPs) were designed. A straightforward method was demonstrated for efficient encapsulation of magnetic NPs into the engineered virus-like particles (VLPs) through the affinity of histidine tags for the methotrexate (MTX)-Ni2+ chelate. HBc144-His VLPs shell could protect Fe3O4-MTX NPs from the recognition by the reticuloendothelial system as well as could increase their cellular uptake efficiency. Through our well-designed tactic, the photothermal efficiency of Fe3O4 NPs were obviously improved in vitro and in vivo upon near-infrared (NIR) laser irradiation. Moreover, Magnetic resonance imaging (MRI) results showed that the Fe3O4-MTX@HBc core-shell NPs were reliable T2-type MRI contrast agents for tumor imaging. Hence the Fe3O4-MTX@HBc core-shell NPs may act as a promising theranostic platform for multimodal cancer treatment.
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Affiliation(s)
- Qiang Zhang
- School of Pharmaceutical Sciences, Xiamen University, Xiamen 361002, Fujian, P. R. China
| | - Wenjun Shan
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Chaochao Ai
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Zhiwei Chen
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance Research, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Tiantian Zhou
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance Research, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Xiaolin Lv
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Xi Zhou
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Shefang Ye
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China
| | - Lei Ren
- Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, Fujian, P. R. China.,Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen University, Xiamen 361005, Fujian, P. R. China.,State Key Lab of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen 361005, P. R. China
| | - Xiumin Wang
- School of Pharmaceutical Sciences, Xiamen University, Xiamen 361002, Fujian, P. R. China
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Low immunogenic bio-nanocapsule based on hepatitis B virus escape mutants. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2017; 14:595-600. [PMID: 29175598 DOI: 10.1016/j.nano.2017.11.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/22/2017] [Accepted: 11/15/2017] [Indexed: 12/31/2022]
Abstract
Bio-nanocapsules (BNCs) consisting of hepatitis B virus surface antigen (HBsAg) L proteins and phospholipids are used as efficient non-viral carriers for liver-specific delivery of genes and drugs. Considering the administration to HB vaccinees and HB patients, endogenous anti-HBsAg immunoglobulins (HBIGs) may reduce the delivery efficacy and prevent repetitive administration. Therefore, low immunogenic BNCs were generated by inserting two point mutations in the HBsAg L protein, which were found in HBV escape mutants. Escape mutant-type BNC (emBNC) showed 50% lower HBIG binding capacity than that of parental BNC (wtBNC). It induced HBIG production to a lesser extent than that associated with wtBNC in BALB/c mice. The emBNC could accumulate into human hepatocyte-derived tumor in mice pre-treated with HBIGs. The complex of emBNC and cationic liposomes could deliver plasmid DNA to HepG2 cells efficiently in the presence of HBIGs. Thus, emBNC could evade HBIG-neutralizing antibodies, expanding the clinical utility of BNC-based nanomedicine.
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Somiya M, Liu Q, Kuroda S. Current Progress of Virus-mimicking Nanocarriers for Drug Delivery. Nanotheranostics 2017; 1:415-429. [PMID: 29188175 PMCID: PMC5704007 DOI: 10.7150/ntno.21723] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 10/09/2017] [Indexed: 12/14/2022] Open
Abstract
Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity).
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Affiliation(s)
| | | | - Shun'ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
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Zhan Z, Zhang X, Huang J, Huang Y, Huang Z, Pan X, Quan G, Liu H, Wang L, Wu AC. Improved Gene Transfer with Functionalized Hollow Mesoporous Silica Nanoparticles of Reduced Cytotoxicity. MATERIALS (BASEL, SWITZERLAND) 2017; 10:731. [PMID: 28773087 PMCID: PMC5551774 DOI: 10.3390/ma10070731] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 06/01/2017] [Accepted: 06/02/2017] [Indexed: 01/27/2023]
Abstract
Gene therapy is a promising strategy for treatment of genetically caused diseases. Successful gene delivery requires an efficient carrier to transfer the desired gene into host cells. Recently, mesoporous silica nanoparticles (MSNs) functionalized with 25 kD polyethyleneimine (PEI) were extensively used as gene delivery carriers. However, 25 kD PEI could significantly reduce the safety of the modified MSNs although it is efficient for intracellular delivery of nucleic acids. In addition, limited drug loading remains a challenge for conventional MSNs drug carriers. Hollow mesoporous silica nanoparticles (HMSNs) with high pore volume, tunable pore size, and excellent biocompatibility are attractive alternatives. To make them more efficient, a less toxic 1.8 kD PEI polymer was used to functionalize the HMSNs which have large pore size (~10 nm) and form PEI-HMSNs. Scanning and transmission electron microscopic images showed that HMSNs were spherical in shape and approximately 270 nm in diameter with uniform hollow nanostructures. The maximum loading capacity of green fluorescent protein labeled DNA (GFP-DNA) in PEI-HMSNs was found to be 37.98 mg/g. The loading capacity of PEI-HMSNs was nearly three-fold higher than those of PEI modified solid nanoparticles, indicating that both hollow and large pores contributed to the increase in DNA adsorption. The transfection of GFP-DNA plasmid loaded in PEI-HMSNs was increased two-fold in comparison to that of 25 kD PEI. MTT assays in Lovo cells showed that the cell viability was more than 85% when the concentration of PEI-HMSNs was 120 µg/mL, whereas the cell viability was less than 20% when the 25 kD PEI was used at the same concentration. These results indicated that PEI-HMSNs could be used as a delivery system for nucleic acids due to good biocompatibility, high gene loading capacity, and enhanced gene transfer efficiency.
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Affiliation(s)
- Zhengwen Zhan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Xiaoxu Zhang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Jiayuan Huang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Ying Huang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Zhengwei Huang
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Xin Pan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
- Zhongshan WanYuan New Drug R&D Co., Ltd., Zhongshan 528451, China.
| | - Guilan Quan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
| | - Hu Liu
- School of Pharmacy, Memorial University of Newfoundland, Newfoundland and Labrador, St. John's, NL A1B 3V6, Canada.
| | - Lili Wang
- School of Pharmacy, Memorial University of Newfoundland, Newfoundland and Labrador, St. John's, NL A1B 3V6, Canada.
| | - And Chuanbin Wu
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
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Li H, Onbe K, Liu Q, Iijima M, Tatematsu K, Seno M, Tada H, Kuroda SI. Synthesis and assembly of Hepatitis B virus envelope protein-derived particles in Escherichia coli. Biochem Biophys Res Commun 2017; 490:155-160. [PMID: 28601634 DOI: 10.1016/j.bbrc.2017.06.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 06/06/2017] [Indexed: 01/27/2023]
Abstract
Hepatitis B virus (HBV) envelope particles have been synthesized in eukaryotic cells (e.g., mammalian cells, insect cells, and yeast cells) as an HB vaccine immunogen and drug delivery system (DDS) nanocarrier. Many researchers had made attempts to synthesize the particles in Escherichia coli for minimize the cost and time for producing HBV envelope particles, but the protein was too deleterious to be synthesized in E. coli. In this study, we generated deletion mutants of HBV envelope L protein (389 amino acid residues (aa)) containing three transmembrane domains (TM1, TM2, TM3). The ΔNC mutant spanning from TM2 to N-terminal half of TM3 (from 237 aa to 335 aa) was found as a shortest form showing spontaneous particle formation. After the N-terminal end of ΔNC mutant was optimized by the N-end rule for E. coli expression, the modified ΔNC mutant (mΔNC) was efficiently expressed as particles in E. coli. The molecular mass of mΔNC particle was approx. 670 kDa, and the diameter was 28.5 ± 6.2 nm (mean ± SD, N = 61). The particle could react with anti-HBV envelope S protein antibody, indicating the particles exhibited S antigenic domain outside as well as HBV envelope particles. Taken together, the E. coli-derived mΔNC particles could be used as a substitute of eukaryotic cell-derived HBV envelope particles for versatile applications.
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Affiliation(s)
- Hao Li
- The Institute of Scientific and Industrial Research, Osaka University, Osaka, 567-0047, Japan
| | - Keisuke Onbe
- Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Qiushi Liu
- The Institute of Scientific and Industrial Research, Osaka University, Osaka, 567-0047, Japan
| | - Masumi Iijima
- The Institute of Scientific and Industrial Research, Osaka University, Osaka, 567-0047, Japan
| | - Kenji Tatematsu
- The Institute of Scientific and Industrial Research, Osaka University, Osaka, 567-0047, Japan
| | - Masaharu Seno
- Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Hiroko Tada
- Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan; Advanced Science Research Center, Okayama University, Okayama, 700-8530, Japan.
| | - Shun' Ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Osaka, 567-0047, Japan.
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Sekiba K, Yamagami M, Otsuka M, Suzuki T, Kishikawa T, Ishibashi R, Ohno M, Sato M, Koike K. Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system. Biochem Biophys Res Commun 2017; 486:521-525. [PMID: 28322797 DOI: 10.1016/j.bbrc.2017.03.076] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 03/16/2017] [Indexed: 01/03/2023]
Abstract
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus. Inhibiting microRNA function, which targets the 3' untranslated region of the MICA gene, enhances this activation. These results demonstrate that the combination of Cas9-based transcriptional activators and simultaneous modulation of microRNA function may be a powerful tool for enhancing MICA protein expression and efficient anti-pathogenic cell immunity.
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Affiliation(s)
- Kazuma Sekiba
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mari Yamagami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Tatsunori Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Takahiro Kishikawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Rei Ishibashi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Motoko Ohno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masaya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Scaffolds for oriented and close-packed immobilization of immunoglobulins. Biosens Bioelectron 2017; 89:810-821. [DOI: 10.1016/j.bios.2016.10.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 09/27/2016] [Accepted: 10/03/2016] [Indexed: 02/07/2023]
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Nishimura Y, Ezawa R, Ishii J, Ogino C, Kondo A. Affibody-displaying bio-nanocapsules effective in EGFR, typical biomarker, expressed in various cancer cells. Bioorg Med Chem Lett 2016; 27:336-341. [PMID: 27908760 DOI: 10.1016/j.bmcl.2016.11.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 10/11/2016] [Accepted: 11/11/2016] [Indexed: 01/02/2023]
Abstract
The expression of epidermal growth factor receptor (EGFR) across a wide range of tumor cells has attracted attention for use as a tumor marker in drug delivery systems. Therefore, binding molecules with the ability to target EGFR have been developed. Among them, we focused on affibodies that are binding proteins derived from staphylococcal protein A. By displaying affibody (ZEGFR) binding to EGFR on the surface of a bio-nanocapsule (BNC) derived from a hepatitis B virus (HBV), we developed an altered BNC (ZEGFR-BNC) with a high specificity to EGFR-expressing cells. We considered two different types of ZEGFR (Z955 and Z1907), and found that the Z1907 dimer-displaying BNC ([Z1907]2-BNC) could effectively bind to EGFR-expressing cells and deliver drugs to the cytosol. Since this study showed that [Z1907]2-BNC could target EGFR-expressing cells, we would use this particle as a drug delivery carrier for various cancer cells expressing EGFR.
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Affiliation(s)
- Yuya Nishimura
- Graduate School of Science, Technology and Innovation, Kobe University, Japan.
| | - Ryosuke Ezawa
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Japan.
| | - Jun Ishii
- Graduate School of Science, Technology and Innovation, Kobe University, Japan.
| | - Chiaki Ogino
- Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Japan.
| | - Akihiko Kondo
- Graduate School of Science, Technology and Innovation, Kobe University, Japan; Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Japan.
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Takamatsu S, Shimomura M, Kamada Y, Maeda H, Sobajima T, Hikita H, Iijima M, Okamoto Y, Misaki R, Fujiyama K, Nagamori S, Kanai Y, Takehara T, Ueda K, Kuroda S, Miyoshi E. Core-fucosylation plays a pivotal role in hepatitis B pseudo virus infection: a possible implication for HBV glycotherapy. Glycobiology 2016; 26:1180-1189. [PMID: 27329181 DOI: 10.1093/glycob/cww067] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 06/05/2016] [Accepted: 06/10/2016] [Indexed: 12/17/2022] Open
Abstract
The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection into hepatoma cells. Comprehensive oligosaccharide analysis showed dramatic increases of core fucosylation in HB611 cells, compared with Huh6 cells. Knock down of fucosyltransferase 8 (FUT8) reduced BNC entry into HB611 cells. In contrast, overexpression of FUT8 in Huh6 cells increased BNC entry. Although expression of sodium taurocholate cotransporting polypeptide (NTCP), which is one of HBV receptors was very similar between Huh6 and HB611 cells, proteins coprecipitated with NTCP were dependent on levels of core-fucosylation, suggesting that core-fucosylation regulates BNC entry into hepatoma cells. Our findings demonstrate that core-fucosylation is an important glycosylation for HBV infection of hepatoma cells through HBV-receptor-mediated endocytosis. Down-regulation of core-fucosylation may be a novel target for HBV therapy.
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Affiliation(s)
- Shinji Takamatsu
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
| | - Mayuka Shimomura
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
| | - Yoshihiro Kamada
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan
| | - Haruka Maeda
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
| | - Tomoaki Sobajima
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
| | - Hayato Hikita
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan
| | - Masumi Iijima
- The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihoga-oka Ibaraki, 567-0047, Japan
| | - Yuta Okamoto
- Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan
| | - Ryo Misaki
- Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan
| | - Kazuhito Fujiyama
- Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan
| | - Shushi Nagamori
- Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine
| | - Yoshikatsu Kanai
- Department of Bio-system Pharmacology, Osaka University Graduate School of Medicine
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan
| | - Keiji Ueda
- Department of Microbiology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan
| | - Shun'ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihoga-oka Ibaraki, 567-0047, Japan
| | - Eiji Miyoshi
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka
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Liu Q, Somiya M, Kuroda S. Elucidation of the early infection machinery of hepatitis B virus by using bio-nanocapsule. World J Gastroenterol 2016; 22:8489-8496. [PMID: 27784961 PMCID: PMC5064030 DOI: 10.3748/wjg.v22.i38.8489] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 07/19/2016] [Accepted: 08/05/2016] [Indexed: 02/06/2023] Open
Abstract
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV. Owing to the poor availability and the difficulty of manipulations, including fluorophore encapsulation, it has been nearly impossible to perform biochemical and cytochemical analyses using a substantial amount of HBV. A bio-nanocapsule (BNC), which is a hollow nanoparticle consisting of HBV envelope L protein, was efficiently synthesized in Saccharomyces cerevisiae. Since BNC could encapsulate payloads (drugs, genes, proteins) and specifically enter human hepatic cells utilizing HBV-derived infection machinery, it could be used as a model of HBV infection to elucidate the early infection machinery. Recently, it was demonstrated that the N-terminal sequence of pre-S1 region (from Asn-9 to Gly-24) possesses low pH-dependent fusogenic activity, which might play a crucial role in the endosomal escape of BNC payloads and in the uncoating process of HBV. In this minireview, we describe a model in which each domain of the HBV L protein contributes to attachment onto human hepatic cells through HSPG, initiation of endocytosis, interaction with NTCP in endosomes, and consequent provocation of membrane fusion followed by endosomal escape.
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Somiya M, Liu Q, Yoshimoto N, Iijima M, Tatematsu K, Nakai T, Okajima T, Kuroki K, Ueda K, Kuroda S. Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan. Virology 2016; 497:23-32. [PMID: 27420796 DOI: 10.1016/j.virol.2016.06.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/24/2016] [Accepted: 06/29/2016] [Indexed: 12/30/2022]
Abstract
Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV. Nevertheless, the cellular entry rates of Myr-BNCs and plasma-derived HBV surface antigen (HBsAg) particles were the same as those of BNCs in NTCP-overexpressing HepG2 cells. Moreover, the cellular entry of these particles was mainly driven by heparan sulfate proteoglycan-mediated endocytosis regardless of NTCP expression. Taken together, cell-surface NTCP may not be involved in the cellular uptake of HBV, while presumably intracellular NTCP plays a critical role.
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Affiliation(s)
- Masaharu Somiya
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan; Japan Society for the Promotion of Science, Tokyo 102-0083, Japan
| | - Qiushi Liu
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan
| | - Nobuo Yoshimoto
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Masumi Iijima
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Kenji Tatematsu
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Tadashi Nakai
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Toshihide Okajima
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan
| | - Kazuyuki Kuroki
- Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Ishikawa 920-1192, Japan
| | - Keiji Ueda
- Division of Virology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
| | - Shun'ichi Kuroda
- The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan; Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, Japan.
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Dehaini D, Fang RH, Zhang L. Biomimetic strategies for targeted nanoparticle delivery. Bioeng Transl Med 2016; 1:30-46. [PMID: 29313005 PMCID: PMC5689512 DOI: 10.1002/btm2.10004] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Revised: 04/07/2016] [Accepted: 04/08/2016] [Indexed: 01/02/2023] Open
Abstract
Nanoparticle‐based drug delivery and imaging platforms have become increasingly popular over the past several decades. Among different design parameters that can affect their performance, the incorporation of targeting functionality onto nanoparticle surfaces has been a widely studied subject. Targeted formulations have the ability to improve efficacy and function by positively modulating tissue localization. Many methods exist for creating targeted nanoformulations, including the use of custom biomolecules such as antibodies or aptamers. More recently, a great amount of focus has been placed on biomimetic targeting strategies that leverage targeting interactions found directly in nature. Such strategies, which have been painstakingly selected over time by the process of evolution to maximize functionality, oftentimes enable scientists to forgo the specialized discovery processes associated with many traditional ligands and help to accelerate development of novel nanoparticle formulations. In this review, we categorize and discuss in‐depth recent works in this growing field of bioinspired research.
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Affiliation(s)
- Diana Dehaini
- Dept. of NanoEngineering and Moores Cancer Center University of California San Diego, La Jolla CA 92093
| | - Ronnie H Fang
- Dept. of NanoEngineering and Moores Cancer Center University of California San Diego, La Jolla CA 92093
| | - Liangfang Zhang
- Dept. of NanoEngineering and Moores Cancer Center University of California San Diego, La Jolla CA 92093
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Mutational analysis of hepatitis B virus pre-S1 (9-24) fusogenic peptide. Biochem Biophys Res Commun 2016; 474:406-412. [PMID: 27120459 DOI: 10.1016/j.bbrc.2016.04.125] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 04/23/2016] [Indexed: 12/31/2022]
Abstract
A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i.e., membrane fusion, membrane disruption, and payload release) upon interaction with target LPs. In this study, instead of BNC and HBV, we generated LPs displaying a mutated form of the pre-S1 (9-24) peptide, and performed a membrane disruption assay using target LPs containing pyranine (fluorophore) and p-xylene-bis (N-pyridinium bromide) (DPX) as a quencher. The membrane disruption activity was found to correlate with the hydrophobicity of the whole structure, while the peptide retained a random-coil structure even under low pH condition. One large hydrophobic cluster (I) and one small hydrophobic cluster (II) residing in the peptide would be connected by the protonation of residues D16 and D20, and thereby exhibit strong membrane disruption activity in a low pH-dependent manner. Furthermore, the introduction of a positively charged residue enhanced the activity significantly, suggesting that a sole positively charged residue (H17) may be important for the interaction with target LPs by electrostatic interaction. Collectively, these results suggest that the pre-S1 (9-24) peptide may be involved in the endosomal escape of the BNC's payloads, as well as in the HBV uncoating process.
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Tatematsu K, Iijima M, Yoshimoto N, Nakai T, Okajima T, Kuroda S. Bio-nanocapsules displaying various immunoglobulins as an active targeting-based drug delivery system. Acta Biomater 2016; 35:238-47. [PMID: 26876802 DOI: 10.1016/j.actbio.2016.02.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 01/26/2016] [Accepted: 02/08/2016] [Indexed: 01/05/2023]
Abstract
The bio-nanocapsule (BNC) is an approximately 30-nm particle comprising the hepatitis B virus (HBV) envelope L protein and a lipid bilayer. The L protein harbors the HBV-derived infection machinery; therefore, BNC can encapsulate payloads such as drugs, nucleic acids, and proteins and deliver them into human hepatocytes specifically in vitro and in vivo. To diversify the possible functions of BNC, we generated ZZ-BNC by replacing the domain indispensable for the human hepatotrophic property of BNC (N-terminal region of L protein) with the tandem form of the IgG Fc-binding Z domain of Staphylococcus aureus protein A. Thus, the ZZ-BNC is an active targeting-based drug delivery system (DDS) nanocarrier that depends on the specificity of the IgGs displayed. However, the Z domain limits the animal species and subtypes of IgGs that can be displayed on ZZ-BNC. In this study, we introduced into BNC an Ig κ light chain-binding B1 domain of Finegoldia magna protein L (protein-L B1 domain) and an Ig Fc-binding C2 domain of Streptococcus species protein G (protein-G C2 domain) to produce LG-BNC. The LL-BNC was constructed in a similar way using a tandem form of the protein-L B1 domain. Both LG-BNC and LL-BNC could display rat IgGs, mouse IgG1, human IgG3, and human IgM, all of which not binding to ZZ-BNC, and accumulate in target cells in an antibody specificity-dependent manner. Thus, these BNCs could display a broad spectrum of Igs, significantly improving the prospects for BNCs as active targeting-based DDS nanocarriers. STATEMENT OF SIGNIFICANCE We previously reported that ZZ-BNC, bio-nanocapsule deploying the IgG-binding Z domain of protein A, could display cell-specific antibody in an oriented immobilization manner, and act as an active targeting-based DDS nanocarrier. Since the Z domain can only bind to limited types of Igs, we generated BNCs deploying other Ig-binding domains: LL-BNC harboring the tandem form of Ig-binding domain of protein L, and LG-BNC harboring the Ig binding domains of protein L and protein G sequentially. Both BNCs could display a broader spectrum of Igs than does the ZZ-BNC. When these BNCs displayed anti-CD11c IgG or anti-EGFR IgG, both of which cannot bind to Z domain, they could bind to and then enter their respective target cells.
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Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WCW. Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination. J Control Release 2016; 240:332-348. [PMID: 26774224 DOI: 10.1016/j.jconrel.2016.01.020] [Citation(s) in RCA: 885] [Impact Index Per Article: 98.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 01/04/2016] [Accepted: 01/11/2016] [Indexed: 12/31/2022]
Abstract
30-99% of administered nanoparticles will accumulate and sequester in the liver after administration into the body. This results in reduced delivery to the targeted diseased tissue and potentially leads to increased toxicity at the hepatic cellular level. This review article focuses on the inter- and intra-cellular interaction between nanoparticles and hepatic cells, the elimination mechanism of nanoparticles through the hepatobiliary system, and current strategies to manipulate liver sequestration. The ability to solve the "nanoparticle-liver" interaction is critical to the clinical translation of nanotechnology for diagnosing and treating cancer, diabetes, cardiovascular disorders, and other diseases.
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Affiliation(s)
- Yi-Nan Zhang
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada
| | - Wilson Poon
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada
| | - Anthony J Tavares
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada
| | - Ian D McGilvray
- Multi Organ Transport Program, Toronto General Research Institute, University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; Toronto General Research Institute, University Health Network, 585 University Avenue, Toronto, ON M5G 2N2, Canada
| | - Warren C W Chan
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Department of Chemistry, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Department of Chemical Engineering & Applied Chemistry, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Department of Materials Science and Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
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Ghisaidoobe ABT, Chung SJ. Functionalized protein nanocages as a platform of targeted therapy and immunodetection. Nanomedicine (Lond) 2015; 10:3579-95. [PMID: 26651131 DOI: 10.2217/nnm.15.175] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
To improve the therapeutic/diagnostic potentials of drugs and/or imaging contrast agents, various targeted delivery systems are actively being developed. Especially protein nanocages, hollow and highly symmetrical nanometer-sized cage structures that are self-assembled from multiple protein subunits, are emerging as powerful targeted delivery tools. Their natural abundance, biocompatibility, low toxicity, well defined size and high symmetry are a few of the favorable characteristics which render protein nanocages as near ideal carriers for pharmaceuticals and/or imaging probes. This review aims to highlight current progress in the development and application of protein nanocages in targeted drug delivery approaches with an emphasis on the use of antibodies as targeting motifs to achieve high selectivity toward specific targets.
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Affiliation(s)
| | - Sang J Chung
- Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea
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Somiya M, Kuroda S. Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule. Adv Drug Deliv Rev 2015; 95:77-89. [PMID: 26482188 DOI: 10.1016/j.addr.2015.10.003] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Revised: 09/21/2015] [Accepted: 10/09/2015] [Indexed: 12/21/2022]
Abstract
As drug delivery systems, nanocarriers should be capable of executing the following functions: evasion of the host immune system, targeting to the diseased site, entering cells, escaping from endosomes, and releasing payloads into the cytoplasm. Since viruses perform some or all of these functions, they are considered naturally occurring nanocarriers. To achieve biomimicry of the hepatitis B virus (HBV), we generated the "bio-nanocapsule" (BNC)-which deploys the human hepatocyte-targeting domain, fusogenic domain, and polymerized-albumin receptor domain of HBV envelope L protein on its surface-by overexpressing the L protein in yeast cells. BNCs are capable of delivering various payloads to the cytoplasm of human hepatic cells specifically in vivo, which is achieved via formation of complexes with various materials (e.g., drugs, nucleic acids, and proteins) by electroporation, fusion with liposomes, or chemical modification. In this review, we describe BNC-related technology, discuss retargeting strategies for BNCs, and outline other virus-inspired nanocarriers.
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