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Bian X, Zhou L, Luo Z, Liu G, Hang Z, Li H, Li F, Wen Y. Emerging Delivery Systems for Enabling Precision Nucleic Acid Therapeutics. ACS NANO 2025; 19:4039-4083. [PMID: 39834294 DOI: 10.1021/acsnano.4c11858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/22/2025]
Abstract
Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these therapeutics face numerous challenges in practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations in delivering them specifically to target tissues. To overcome these obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers, exosomes, antibody oligonucleotide conjugates, and DNA nanostructure-based delivery systems. These systems enhance the therapeutic efficacy of nucleic acid drugs by improving their stability, targeting specificity, and half-life in vivo. In this review, we systematically discuss different types of nucleic acid drugs, analyze the major barriers encountered in their delivery, and summarize the current research progress in emerging delivery systems. We also highlight the latest advancements in the application of these systems for treating genetic diseases, infectious diseases, cancer, brain diseases, and wound healing. This review aims to provide a comprehensive overview of nucleic acid drug delivery systems' current status and future directions by integrating the latest advancements in nanotechnology, biomaterials science, and gene editing technologies, emphasizing their transformative potential in precision medicine.
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Affiliation(s)
- Xiaochun Bian
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Liping Zhou
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Zhiwei Luo
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Guotao Liu
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Zhongci Hang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Haohao Li
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
| | - Fengyong Li
- Plastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yongqiang Wen
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China
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2
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Kushwaha N, Panjwani D, Patel S, Ahlawat P, Yadav MR, Patel AS. Emerging advances in nano-biomaterial assisted amyloid beta chimeric antigen receptor macrophages (CAR-M) therapy: reducing plaque burden in Alzheimer's disease. J Drug Target 2025; 33:185-205. [PMID: 39403775 DOI: 10.1080/1061186x.2024.2417012] [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] [Received: 08/04/2024] [Revised: 09/23/2024] [Accepted: 10/08/2024] [Indexed: 10/22/2024]
Abstract
Alzheimer's disease is the most common form, accounting for 60-70% of 55 million dementia cases. Even though the precise pathophysiology of AD is not completely understood, clinical trials focused on antibodies targeting aggregated forms of β amyloid (Aβ) have demonstrated that reducing amyloid plaques can arrest cognitive decline in patients in the early stages of AD. In this study, we provide an overview of current research and innovations for controlled release from nano-biomaterial-assisted chimeric antigen receptor macrophage (CAR-M) therapeutic strategies targeted at AD. Nano-bio materials, such as iron-oxide nanoparticles (IONPs), can be made selectively (Hp-Hb/mannose) to bind and take up Aβ plaques like CAR-M cells. By using nano-bio materials, both the delivery and stability of CAR-M cells in brain tissue can be improved to overcome the barriers of the BBB and enhance therapeutic effects. By enhancing the targeting capabilities and stability of CAR-M cells, mRNA-loaded nano-biomaterials can significantly improve the efficacy of immunotherapy for plaque reduction in AD. This novel strategy holds promise for translating preclinical successes into clinical applications, potentially revolutionising the management of AD.
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Affiliation(s)
- Nishabh Kushwaha
- Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India
| | - Drishti Panjwani
- Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India
| | - Shruti Patel
- Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India
| | - Priyanka Ahlawat
- Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India
| | - Mange Ram Yadav
- Research and Development Cell, Parul University, Vadodara, India
| | - Asha S Patel
- Department of Pharmaceutics, Parul Institute of Pharmacy, Parul University, Vadodara, India
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3
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Dykman L, Khlebtsov B, Khlebtsov N. Drug delivery using gold nanoparticles. Adv Drug Deliv Rev 2025; 216:115481. [PMID: 39617254 DOI: 10.1016/j.addr.2024.115481] [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] [Received: 07/12/2024] [Revised: 11/23/2024] [Accepted: 11/26/2024] [Indexed: 12/16/2024]
Abstract
Modern nanotechnologies provide various possibilities for efficiently delivering drugs to biological targets. This review focuses on using functionalized gold nanoparticles (GNPs) as a drug delivery platform. Owing to their exceptional size and surface characteristics, GNPs are a perfect drug delivery vehicle for targeted and selective distribution. Several in vitro and in vivo tests have shown how simple it is to tailor these particles to administer chemical medications straight to tumors. The GNP surface can also be coated with ligands to modify drug release or improve selectivity. Moreover, the pharmacological activity can be enhanced by using the photothermal characteristics of the particles.
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Affiliation(s)
- Lev Dykman
- Institute of Biochemistry and Physiology of Plants and Microorganisms, "Saratov Scientific Centre of the Russian Academy of Sciences", 13 Prospekt Entuziastov, Saratov 410049, Russia
| | - Boris Khlebtsov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, "Saratov Scientific Centre of the Russian Academy of Sciences", 13 Prospekt Entuziastov, Saratov 410049, Russia
| | - Nikolai Khlebtsov
- Institute of Biochemistry and Physiology of Plants and Microorganisms, "Saratov Scientific Centre of the Russian Academy of Sciences", 13 Prospekt Entuziastov, Saratov 410049, Russia; Saratov State University, 83 Ulitsa Astrakhanskaya, Saratov 410012, Russia.
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Mavi AK, Kumar M, Singh A, Prajapati MK, Khabiya R, Maru S, Kumar D. Progress in Non‐Viral Delivery of Nucleic Acid. INTEGRATION OF BIOMATERIALS FOR GENE THERAPY 2023:281-322. [DOI: 10.1002/9781394175635.ch10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Cojocaru E, Ghitman J, Stan R. Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine. Polymers (Basel) 2022; 14:2647. [PMID: 35808692 PMCID: PMC9269101 DOI: 10.3390/polym14132647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/23/2022] [Accepted: 06/25/2022] [Indexed: 11/25/2022] Open
Abstract
Gene-based therapy represents the latest advancement in medical biotechnology. The principle behind this innovative approach is to introduce genetic material into specific cells and tissues to stimulate or inhibit key signaling pathways. Although enormous progress has been achieved in the field of gene-based therapy, challenges connected to some physiological impediments (e.g., low stability or the inability to pass the cell membrane and to transport to the desired intracellular compartments) still obstruct the exploitation of its full potential in clinical practices. The integration of gene delivery technologies with electrospun fibrous architectures represents a potent strategy that may tackle the problems of stability and local gene delivery, being capable to promote a controlled and proficient release and expression of therapeutic genes in the targeted cells, improving the therapeutic outcomes. This review aims to outline the impact of electrospun-fibrous-architecture-mediated gene therapy drug delivery, and it emphatically discusses the latest advancements in their formulation and the therapeutic outcomes of these systems in different fields of regenerative medicine, along with the main challenges faced towards the translation of promising academic results into tangible products with clinical application.
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Affiliation(s)
- Elena Cojocaru
- Advanced Polymer Materials Group, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania;
| | - Jana Ghitman
- Advanced Polymer Materials Group, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania;
| | - Raluca Stan
- Department of Organic Chemistry “C. Nenitzescu”, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania;
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Mendes BB, Conniot J, Avital A, Yao D, Jiang X, Zhou X, Sharf-Pauker N, Xiao Y, Adir O, Liang H, Shi J, Schroeder A, Conde J. Nanodelivery of nucleic acids. NATURE REVIEWS. METHODS PRIMERS 2022; 2:24. [PMID: 35480987 PMCID: PMC9038125 DOI: 10.1038/s43586-022-00104-y] [Citation(s) in RCA: 293] [Impact Index Per Article: 97.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/09/2022] [Indexed: 12/11/2022]
Abstract
There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting. Nucleic acid therapeutics such as antisense DNA, mRNA, small interfering RNA (siRNA) or microRNA (miRNA) have been widely explored to modulate DNA or RNA expression Strikingly, gene therapies combined with nanoscale delivery systems have broadened the therapeutic and biomedical applications of these molecules, such as bioanalysis, gene silencing, protein replacement and vaccines. Here, we overview how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. It is crucial to outline some of the general design considerations of nucleic acid delivery nanoparticles, their extraordinary properties and the structure-function relationships of these nanomaterials with biological systems and diseased cells and tissues.
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Affiliation(s)
- Bárbara B Mendes
- NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - João Conniot
- NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Aviram Avital
- Department of Chemical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
- The Norman Seiden Multidisciplinary Program for Nanoscience and Nanotechnology, Technion - Israel Institute of Technology, Haifa, Israel
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Dongbao Yao
- Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), University of Science and Technology of China, Hefei, Anhui, People's Republic of China
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Xingya Jiang
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Xiang Zhou
- Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), University of Science and Technology of China, Hefei, Anhui, People's Republic of China
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Noga Sharf-Pauker
- Department of Chemical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
- The Norman Seiden Multidisciplinary Program for Nanoscience and Nanotechnology, Technion - Israel Institute of Technology, Haifa, Israel
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Yuling Xiao
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Omer Adir
- Department of Chemical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
- The Norman Seiden Multidisciplinary Program for Nanoscience and Nanotechnology, Technion - Israel Institute of Technology, Haifa, Israel
- These authors contributed equally: Bárbara B. Mendes, João Conniot, Aviram Avital, Dongbao Yao, Xingya Jiang, Xiang Zhou, Noga Sharf-Pauker, Yuling Xiao, Omer Adir
| | - Haojun Liang
- Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), University of Science and Technology of China, Hefei, Anhui, People's Republic of China
| | - Jinjun Shi
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Avi Schroeder
- Department of Chemical Engineering, Technion - Israel Institute of Technology, Haifa, Israel
| | - João Conde
- NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
- Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
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Gantenbein B, Tang S, Guerrero J, Higuita-Castro N, Salazar-Puerta AI, Croft AS, Gazdhar A, Purmessur D. Non-viral Gene Delivery Methods for Bone and Joints. Front Bioeng Biotechnol 2020; 8:598466. [PMID: 33330428 PMCID: PMC7711090 DOI: 10.3389/fbioe.2020.598466] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use.
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Affiliation(s)
- Benjamin Gantenbein
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Shirley Tang
- Department of Biomedical Engineering and Department of Orthopaedics, Spine Research Institute Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Julien Guerrero
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Natalia Higuita-Castro
- Department of Biomedical Engineering and Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Ana I Salazar-Puerta
- Department of Biomedical Engineering and Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Andreas S Croft
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Amiq Gazdhar
- Department of Pulmonary Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Devina Purmessur
- Department of Biomedical Engineering and Department of Orthopaedics, Spine Research Institute Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
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Rahman M, Alharbi KS, Alruwaili NK, Anfinan N, Almalki WH, Padhy I, Sambamoorthy U, Swain S, Beg S. Nucleic acid-loaded lipid-polymer nanohybrids as novel nanotherapeutics in anticancer therapy. Expert Opin Drug Deliv 2020; 17:805-816. [DOI: 10.1080/17425247.2020.1757645] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Mahfoozur Rahman
- Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India
| | - Khalid S. Alharbi
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia
| | - Nabil K. Alruwaili
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakakah, Saudi Arabia
| | - Nisrin Anfinan
- Department of Obstetrics and Gynecology, Gynecology Oncology Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Waleed H. Almalki
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ipsa Padhy
- Department of Pharmaceutical Analysis and Quality Assurance, School of Pharmaceutical Education and Research, Berhampur University, Berhampur, Odisha, India
| | - Unnam Sambamoorthy
- Department of Pharmaceutics, NRI College of Pharmacy, NRI Group of Institutions, Krishna District, India
| | - Suryakanta Swain
- Southern Institute of Medical Sciences, College of Pharmacy, Department of Pharmaceutics, SIMS Group of Institutions, Guntur, India
| | - Sarwar Beg
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
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9
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Xiao YP, Zhang J, Liu YH, Huang Z, Guo Y, Yu XQ. Bioinspired pyrimidine-containing cationic polymers as effective nanocarriers for DNA and protein delivery. J Mater Chem B 2020; 8:2275-2285. [PMID: 32100787 DOI: 10.1039/c9tb02528f] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure-activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of β-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.
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Affiliation(s)
- Ya-Ping Xiao
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
| | - Ji Zhang
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
| | - Yan-Hong Liu
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
| | - Zheng Huang
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
| | - Yu Guo
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
| | - Xiao-Qi Yu
- Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
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10
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Patil S, Gao YG, Lin X, Li Y, Dang K, Tian Y, Zhang WJ, Jiang SF, Qadir A, Qian AR. The Development of Functional Non-Viral Vectors for Gene Delivery. Int J Mol Sci 2019; 20:E5491. [PMID: 31690044 PMCID: PMC6862238 DOI: 10.3390/ijms20215491] [Citation(s) in RCA: 164] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 10/22/2019] [Accepted: 11/01/2019] [Indexed: 01/06/2023] Open
Abstract
Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.
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Affiliation(s)
- Suryaji Patil
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Yong-Guang Gao
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Xiao Lin
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Yu Li
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Kai Dang
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Ye Tian
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Wen-Juan Zhang
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Shan-Feng Jiang
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Abdul Qadir
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
| | - Ai-Rong Qian
- Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
- Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University Xi'an 710072, China.
- NPU-UAB Joint Laboratory for Bone Metabolism, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China.
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Enhancing Curcumin Oral Bioavailability Through Nanoformulations. Eur J Drug Metab Pharmacokinet 2019; 44:459-480. [DOI: 10.1007/s13318-019-00545-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Perri V, Pellegrino M, Ceccacci F, Scipioni A, Petrini S, Gianchecchi E, Lo Russo A, De Santis S, Mancini G, Fierabracci A. Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes. PLoS One 2017; 12:e0175784. [PMID: 28437437 PMCID: PMC5402975 DOI: 10.1371/journal.pone.0175784] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 04/01/2017] [Indexed: 12/13/2022] Open
Abstract
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target. We aimed to develop novel wild type PTPN22 short interfering RNA duplexes (siRNA) and optimize their delivery into Jurkat T cells and PBMC by using liposomal carriers. Conformational stability, size and polydispersion of siRNA in lipoplexes was measured by CD spectroscopy and DLS. Lipoplexes internalization and toxicity evaluation was assessed by confocal microscopy and flow cytometry analysis. Their effect on Lyp expression was evaluated by means of Western Blot and confocal microscopy. Functional assays through engagement of TCR signaling were established to evaluate biological consequences of down-modulation. Both Jurkat T cells and PBMC were efficiently transfected by stable custom lipoplexes. Jurkat T cell morphology and proliferation was not affected. Lipoplexes incorporation was visualized in CD3+ but also in CD3- peripheral blood immunotypes without signs of toxicity, damage or apoptosis. Efficacy in affecting Lyp protein expression was demonstrated in both transfected Jurkat T cells and PBMC. Moreover, impairment of Lyp inhibitory activity was revealed by increase of IL-2 secretion in culture supernatants of PBMC following anti-CD3/CD28 T cell receptor-driven stimulation. The results of our study open the pathway to future trials for the treatment of autoimmune diseases based on the selective inhibition of variant PTPN22 allele using lipoplexes of siRNA antisense oligomers.
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Affiliation(s)
- Valentina Perri
- Type 1 Diabetes Centre, Infectivology and Clinical Trials Area, Children’s Hospital Bambino Gesù, Rome, Italy
| | - Marsha Pellegrino
- Type 1 Diabetes Centre, Infectivology and Clinical Trials Area, Children’s Hospital Bambino Gesù, Rome, Italy
| | - Francesca Ceccacci
- CNR Chemical Methodologies Institute-Section Mechanisms of reaction (CNR-IMC-SMR) c/o Sapienza University, Rome, Italy
| | - Anita Scipioni
- Department of Chemistry, Sapienza University, Rome, Italy
| | - Stefania Petrini
- Confocal Microscopy Core Facility, Research Laboratories, Children’s Hospital Bambino Gesù, Rome, Italy
| | - Elena Gianchecchi
- Type 1 Diabetes Centre, Infectivology and Clinical Trials Area, Children’s Hospital Bambino Gesù, Rome, Italy
| | - Anna Lo Russo
- Type 1 Diabetes Centre, Infectivology and Clinical Trials Area, Children’s Hospital Bambino Gesù, Rome, Italy
| | | | | | - Alessandra Fierabracci
- Type 1 Diabetes Centre, Infectivology and Clinical Trials Area, Children’s Hospital Bambino Gesù, Rome, Italy
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