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1
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Kabil MF, Gaber SAA, Hamzawy MA, El-Sherbiny IM, Nasr M. Folic/lactobionic acid dual-targeted polymeric nanocapsules for potential treatment of hepatocellular carcinoma. Drug Deliv Transl Res 2024; 14:1338-1351. [PMID: 37930630 DOI: 10.1007/s13346-023-01467-9] [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] [Accepted: 10/28/2023] [Indexed: 11/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor that affects many patients diagnosed with hepatic cell inflammation and liver cirrhosis. Targeted polymeric nanocapsules could facilitate the internalization and accumulation of anticancer drugs. Dual-targeted folic acid/lactobionic acid-poly lactic co-glycolic acid nanocapsules (NCs) were prepared and loaded with pterostilbene (PTN) and characterized for their physicochemical properties, as well as in vitro and in vivo anticancer activity. NCs displayed a size of 222 nm, zeta potential of - 16.5 mV, and sustained release for 48 h. The IC50 of PTN NCs (5.87 ± 0.8 µg/mL) was 20 times lower than unencapsulated PTN (121.26 ± 9.42 µg/mL) on HepG2 liver cancer cells owing to the enhanced cellular uptake of the former, as delineated by flow cytometry. In vivo study on HCC-induced animals delineated the superiority of the dual-targeted NCs over the unencapsulated PTN, which significantly reduced the liver markers ALT, AST, and ALP, as well as the tumor-related markers AFP and Bcl2, and elevated the anti-apoptotic marker caspase 3. Furthermore, the NCs significantly reduced the oxidative stress and exhibited almost comparable histological features to the normal group. Therefore, it can be concluded that the dual-ligated folic acid/lactobionic acid nanocapsules can be considered a promising potential treatment option for hepatocellular carcinoma.
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Affiliation(s)
- Mohamed Fawzi Kabil
- Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, Giza, Egypt
| | - Sara A Abdel Gaber
- Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafr Elsheikh University, Kafr Elsheikh, Egypt
| | - Mohamed A Hamzawy
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt
| | - Ibrahim M El-Sherbiny
- Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, Giza, Egypt
| | - Maha Nasr
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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Razmimanesh F, Sodeifian G. Evaluation of a temperature-responsive magnetotocosome as a magnetic targeting drug delivery system for sorafenib tosylate anticancer drug. Heliyon 2023; 9:e21794. [PMID: 38027677 PMCID: PMC10658271 DOI: 10.1016/j.heliyon.2023.e21794] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/15/2023] [Accepted: 10/28/2023] [Indexed: 12/01/2023] Open
Abstract
In this investigation, a polymeric fusion of chitosan (CS) and thermosensitive poly (N-isopropyl acrylamide) - PNIPAAm - encapsulated a magnetotocosome, biocompatible nanocarrier. This encapsulation strategy demonstrated improved drug entrapment efficiency, achieving up to 98.8 %. Additionally, it exhibited extended stability, optimal particle dimensions, and the potential for industrial scaling, thus facilitating controlled drug delivery of sorafenib tosylate to cancerous tissue. Reversible Addition-Fragmentation Chain Transfer (RAFT) techniques were employed to synthesize PNIPAAm. The effects of polymer molecular weight and polydispersity index on the lower critical solution temperature (LCST) were evaluated. The resulting polymeric amalgamation, involving the thermosensitive PNIPAAm synthesized using RAFT techniques and CS that coated the magnetotocosome (CS-Raft PNIPAAm-magnetotocosome) with an LCST approximately at 45 °C, holds the potential to enhance drug bioavailability and enable applications in hyperthermia treatment, controlled release, and targeted drug delivery.
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Affiliation(s)
- Fariba Razmimanesh
- Department of Chemical Engineering, Faculty of Engineering, University of Kashan, 87317-53153, Kashan, Iran
- Laboratory of Biotechnology and Nanotechnology, University of Kashan, 87317-53153, Kashan, Iran
- Biotechnology Centre, Faculty of Engineering, University of Kashan, 87317-53153, Kashan, Iran
| | - Gholamhossein Sodeifian
- Department of Chemical Engineering, Faculty of Engineering, University of Kashan, 87317-53153, Kashan, Iran
- Laboratory of Biotechnology and Nanotechnology, University of Kashan, 87317-53153, Kashan, Iran
- Biotechnology Centre, Faculty of Engineering, University of Kashan, 87317-53153, Kashan, Iran
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3
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Wang L, Chen M, Ran X, Tang H, Cao D. Sorafenib-Based Drug Delivery Systems: Applications and Perspectives. Polymers (Basel) 2023; 15:2638. [PMID: 37376284 DOI: 10.3390/polym15122638] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/02/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
As a Food and Drug Administration (FDA)-approved molecular-targeted chemotherapeutic drug, sorafenib (SF) can inhibit angiogenesis and tumor cell proliferation, leading to improved patient overall survival of hepatocellular carcinoma (HCC). In addition, SF is an oral multikinase inhibitor as a single-agent therapy in renal cell carcinoma. However, the poor aqueous solubility, low bioavailability, unfavorable pharmacokinetic properties and undesirable side effects (anorexia, gastrointestinal bleeding, and severe skin toxicity, etc.) seriously limit its clinical application. To overcome these drawbacks, the entrapment of SF into nanocarriers by nanoformulations is an effective strategy, which delivers SF in a target tumor with decreased adverse effects and improved treatment efficacy. In this review, significant advances and design strategies of SF nanodelivery systems from 2012 to 2023 are summarized. The review is organized by type of carriers including natural biomacromolecule (lipid, chitosan, cyclodextrin, etc.); synthetic polymer (poly(lactic-co-glycolic acid), polyethyleneimine, brush copolymer, etc.); mesoporous silica; gold nanoparticles; and others. Co-delivery of SF and other active agents (glypican-3, hyaluronic acid, apolipoprotein peptide, folate, and superparamagnetic iron oxide nanoparticles) for targeted SF nanosystems and synergistic drug combinations are also highlighted. All these studies showed promising results for targeted treatment of HCC and other cancers by SF-based nanomedicines. The outlook, challenges and future opportunities for the development of SF-based drug delivery are presented.
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Affiliation(s)
- Lingyun Wang
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641, China
| | - Meihuan Chen
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641, China
| | - Xueguang Ran
- Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South China, State Key Laboratory of Livestock and Poultry Breeding, Guangzhou 510641, China
| | - Hao Tang
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641, China
| | - Derong Cao
- Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510641, China
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4
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Guo S, Zheng L, He W, Chai C, Chen X, Ma S, Wang N, Choi MM, Bian W. S,O-doped carbon nitride as a fluorescence probe for the label-free detection of folic acid and targeted cancer cell imaging. ARAB J CHEM 2022. [DOI: 10.1016/j.arabjc.2022.104520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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5
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Sun Y, Xue Z, Huang T, Che X, Wu G. Lipid metabolism in ferroptosis and ferroptosis-based cancer therapy. Front Oncol 2022; 12:941618. [PMID: 35978815 PMCID: PMC9376317 DOI: 10.3389/fonc.2022.941618] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/08/2022] [Indexed: 11/28/2022] Open
Abstract
Ferroptosis refers to iron-dependent, specialized, and regulated-necrosis mediated by lipid peroxidation, which is closely related to a variety of diseases, including cancer. Tumor cells undergo extensive changes in lipid metabolism, including lipid peroxidation and ferroptosis. Changes in lipid metabolism are critical for the regulation of ferroptosis and thus have important roles in cancer therapy. In this review, we introduce the characteristics of ferroptosis and briefly analyze the links between several metabolic mechanisms and ferroptosis. The effects of lipid peroxides, several signaling pathways, and the molecules and pathways involved in lipid metabolism on ferroptosis were extensively analyzed. Finally, our review highlights some ferroptosis-based treatments and presents some methods and examples of how these treatments can be combined with other treatments.
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Affiliation(s)
- Yonghao Sun
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zuoxing Xue
- Department of Urology, Dalian University Affiliated Xinhua Hospital, Dalian, China
| | - Tao Huang
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiangyu Che
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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6
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Stăncioiu L, Gherman AMR, Brezeștean I, Dina NE. Vibrational spectral analysis of Sorafenib and its molecular docking study compared to other TKIs. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.131507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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7
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Li JY, Liu SQ, Yao RQ, Tian YP, Yao YM. A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis. Front Cell Dev Biol 2021; 9:799499. [PMID: 34926476 PMCID: PMC8675329 DOI: 10.3389/fcell.2021.799499] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 11/15/2021] [Indexed: 12/25/2022] Open
Abstract
Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.
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Affiliation(s)
- Jing-yan Li
- Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shuang-qing Liu
- Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Ren-qi Yao
- Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Ying-ping Tian
- Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- *Correspondence: Ying-ping Tian, ; Yong-ming Yao,
| | - Yong-ming Yao
- Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
- *Correspondence: Ying-ping Tian, ; Yong-ming Yao,
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8
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Wang J, Lv F, Sun T, Zhao S, Chen H, Liu Y, Liu Z. Sorafenib Nanomicelles Effectively Shrink Tumors by Vaginal Administration for Preoperative Chemotherapy of Cervical Cancer. NANOMATERIALS 2021; 11:nano11123271. [PMID: 34947619 PMCID: PMC8705954 DOI: 10.3390/nano11123271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/28/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022]
Abstract
To investigate the potential of sorafenib (SF) in preoperative chemotherapy for cervical cancer to reduce tumor volume, sorafenib micelles (SF micelles) with good stability and high drug loading were designed. SF micelles were prepared by film hydration followed by the ultrasonic method. The results showed that the SF micelles were spherical with an average particle size of 67.18 ± 0.66 nm (PDI 0.17 ± 0.01), a considerable drug loading of 15.9 ± 0.46% (w/w%) and satisfactory stability in buffers containing plasma or not for at least 2 days. In vitro release showed that SF was gradually released from SF micelles and almost completely released on the third day. The results of in vitro cellular intake, cytotoxicity and proliferation of cervical cancer cell TC-1 showed that SF micelles were superior to sorafenib (Free SF). For intravaginal administration, SF micelles were dispersed in HPMC (SF micelles/HPMC), showed good viscosity sustained-release profiles in vitro and exhibited extended residence in intravaginal in vivo. Compared with SF micelles dispersed in N.S. (SF micelles/N.S.), SF micelles/HPMC significantly reduced tumor size with a tumor weight inhibition rate of 73%. The results suggested that SF micelles had good potential for preoperative tumor shrinkage and improving the quality life of patients.
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Affiliation(s)
- Jun Wang
- Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China;
| | - Fengmei Lv
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (F.L.); (T.S.); (S.Z.); (H.C.)
| | - Tao Sun
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (F.L.); (T.S.); (S.Z.); (H.C.)
| | - Shoujin Zhao
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (F.L.); (T.S.); (S.Z.); (H.C.)
| | - Haini Chen
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (F.L.); (T.S.); (S.Z.); (H.C.)
| | - Yu Liu
- Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China;
- Correspondence: (Y.L.); (Z.L.)
| | - Zhepeng Liu
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; (F.L.); (T.S.); (S.Z.); (H.C.)
- Correspondence: (Y.L.); (Z.L.)
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9
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Arafa KK, Fytory M, Mousa SA, El-Sherbiny IM. Nanosized biligated metal-organic framework systems for enhanced cellular and mitochondrial sequential targeting of hepatic carcinoma. Biomater Sci 2021; 9:6609-6622. [PMID: 34582539 DOI: 10.1039/d1bm01247a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Mitochondria are reported to play a paramount role in tumorigenesis which positions them as an instrumental druggable target. However, selective drug delivery to cancer-localized mitochondria remains challenging. Herein, we report for the first time, the design, development and evaluation of a hepatic cancer-specific mitochondria-targeted dual ligated nanoscale metal-organic framework (NMOF) for cellular and mitochondrial sequential drug delivery. Surface functionalization was performed through covalent-linking of folic acid and triphenylphosphonium moieties to the aminated Zr-based MOF, NH2-UiO-66. The characterization of the dual-ligated NMOFs using XRD, FTIR, DSC and BET analysis proved the successful conjugation process. Assessment of the drug loading and release profiling of doxorubicin (DOX)-loaded NMOF confirmed the proper retention of the drug within the NMOF porous structure alongside enhanced release in the tumor acidic environment. Furthermore, biological evaluation of the anti-tumor activity of the DOX-loaded dual-ligated NMOF on hepatocellular carcinoma affirmed the superiority of the developed system in killing the cancerous cells via apoptosis induction and halting cell cycle progression. This study attempts to underscore the promising potential of surface functionalized NMOFs in developing anticancer drug delivery systems to achieve targeted therapy.
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Affiliation(s)
- Kholoud K Arafa
- Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza 12578, Egypt.
| | - Mostafa Fytory
- Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza 12578, Egypt.
| | - Shaker A Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
| | - Ibrahim M El-Sherbiny
- Nanomedicine Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza 12578, Egypt.
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10
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Khalil HH, Osman HA, Teleb M, Darwish AI, Abu-Serie MM, Khattab SN, Haiba NS. Engineered s-Triazine-Based Dendrimer-Honokiol Conjugates as Targeted MMP-2/9 Inhibitors for Halting Hepatocellular Carcinoma. ChemMedChem 2021; 16:3701-3719. [PMID: 34547831 DOI: 10.1002/cmdc.202100465] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 09/20/2021] [Indexed: 12/17/2022]
Abstract
Despite the advances in developing MMP-2/9 inhibitors, off-target side effects and pharmacokinetics problems remain major challenges hindering their clinical success in cancer therapy. However, recent targeting strategies have clearly revitalized MMP research. Herein, we introduce new s-triazine-based dendrimers endowed with intrinsic MMP-2/9 inhibitory potential and tetherable to hepatocellular carcinoma-specific targeting ligands and anticancer agents via biodegradable linkages for targeted therapy. The designed dendrimeric platform was built with potential zinc-binding branching linkers (hydrazides) and termini (carboxylic acids and hydrazides) to confer potency against MMP-2/9. Preliminary cytotoxicity screening and MMP-2/9 inhibition assay of the free dendrimers revealed promising potency (MMP-9; IC50 =0.35-0.57 μM, MMP-2; IC50 =0.39-0.77 μM) within their safe doses (EC100 =94.15-42.75 μM). The hydrazide dendrimer was comparable to NNGH and superior to the carboxylic acid analogue. MTT assay showed that the free dendrimers were superior to the reference anticancer agent honokiol. Their anticancer potency was enhanced by HK conjugation, targeting ligands installation and PEGylation as exemplified by the hydrazide dendrimer conjugate (TPG3 -NH2 )-SuHK-FA-SuPEG (Huh-7; IC50 =5.54 μM, HepG-2; IC50 =10.07 μM) being 4 folds more active than HK, followed by the carboxylic acid conjugate (TPG3 -OH)-HK-LA-PEG (Huh-7; IC50 =14.97, HepG-2; IC50 =21.29 μM). This was consistent with apoptosis studies.
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Affiliation(s)
- Hosam H Khalil
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt
| | - Heba A Osman
- Department of Physics and Chemistry Faculty of Education, Alexandria University, Alexandria, 21526, Egypt
| | - Mohamed Teleb
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - A I Darwish
- Department of Physics and Chemistry Faculty of Education, Alexandria University, Alexandria, 21526, Egypt
| | - Marwa M Abu-Serie
- Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute City of Scientific Research and Technological Applications (SRTA-City), Alexandria, 21934, Egypt
| | - Sherine N Khattab
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt.,Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Nesreen S Haiba
- Department of Physics and Chemistry Faculty of Education, Alexandria University, Alexandria, 21526, Egypt
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11
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Chen Y, Fan H, Wang S, Tang G, Zhai C, Shen L. Ferroptosis: A Novel Therapeutic Target for Ischemia-Reperfusion Injury. Front Cell Dev Biol 2021; 9:688605. [PMID: 34447746 PMCID: PMC8384466 DOI: 10.3389/fcell.2021.688605] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 07/20/2021] [Indexed: 12/13/2022] Open
Abstract
Ischemia-reperfusion (I/R) injury is a major cause of cell death and organ damage in numerous pathologies, including myocardial infarction, stroke, and acute kidney injury. Current treatment methods for I/R injury are limited. Ferroptosis, which is a newly uncovered type of regulated cell death characterized by iron overload and lipid peroxidation accumulation, has been investigated in various diseases. There is increasing evidence of a close association between ferroptosis and I/R injury, with ferroptosis frequently identified as a new therapeutic target for the management of I/R injury. This review summarizes the current status of ferroptosis and discusses its relationship with I/R injury, as well as potential treatment strategies targeting it.
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Affiliation(s)
- Yunqing Chen
- Department of Infectious Disease, The Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Hongyan Fan
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Shijun Wang
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Guanmin Tang
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Changlin Zhai
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, China
| | - Liang Shen
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Jiaxing, China
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Hu H, Chen Y, Jing L, Zhai C, Shen L. The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment. Front Cardiovasc Med 2021; 8:710963. [PMID: 34368260 PMCID: PMC8341300 DOI: 10.3389/fcvm.2021.710963] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 06/21/2021] [Indexed: 12/24/2022] Open
Abstract
Ferroptosis is an iron-dependent cell death, which is characterized by iron overload and lipid peroxidation. Ferroptosis is distinct from apoptosis, necroptosis, autophagy, and other types of cell death in morphology and function. Ferroptosis is regulated by a variety of factors and controlled by several mechanisms, including mitochondrial activity and metabolism of iron, lipid, and amino acids. Accumulating evidence shows that ferroptosis is closely related to a majority of cardiovascular diseases (CVDs), including cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, heart failure, and atherosclerosis. This review summarizes the current status of ferroptosis and discusses ferroptosis as a potential therapeutic target for CVDs.
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Affiliation(s)
- Huilin Hu
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Zhejiang, China
| | - Yunqing Chen
- Department of Infection, The Affiliated Hospital of Jiaxing University, Zhejiang, China
| | - Lele Jing
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Zhejiang, China
| | - Changlin Zhai
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Zhejiang, China
| | - Liang Shen
- Department of Cardiology, The Affiliated Hospital of Jiaxing University, Zhejiang, China
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Kumar V, Rahman M, Gahtori P, Al-Abbasi F, Anwar F, Kim HS. Current status and future directions of hepatocellular carcinoma-targeted nanoparticles and nanomedicine. Expert Opin Drug Deliv 2021; 18:673-694. [PMID: 33295218 DOI: 10.1080/17425247.2021.1860939] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is a major health problem worldwide. Conventional therapies covering either chemotherapy or combination therapy still have sub-optimal responses with significant adverse effects and toxicity. Moreover, tumor cells usually acquire resistance quickly for traditional approaches, limiting their use in HCC. Interest in nanomedicine due to minimal systemic toxicity and a high degree of target-specific drug-delivery have pulled the attention of health scientists in this area of therapeutics. AREA COVERED The review covers the incidence and epidemiology of HCC, proposed molecular drug targets, mechanistic approach and emergence of nanomedicines including nanoparticles, lipidic nanoparticles, vesicular-based nanocarrier, virus-like particles with momentous therapeutic aspects including biocompatibility, and toxicity of nanocarriers along with conclusions and future perspective, with an efficient approach to safely cross physiological barriers to reach the target site for treating liver cancer. EXPERT OPINION Remarkable outcomes have recently been observed for the therapeutic efficacy of nanocarriers with respect to a specific drug target against the treatment of HCC by existing under trial drugs.
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Affiliation(s)
- Vikas Kumar
- Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Shalom Institute of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India
| | - Mahfoozur Rahman
- Natural Product Drug Discovery Laboratory, Department of Pharmaceutical Sciences, Shalom Institute of Health Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad, India
| | - Prashant Gahtori
- School of Pharmacy, Graphic Era Hill University Dehradun 248002, Uttarakhand, India
| | - Fahad Al-Abbasi
- Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Firoz Anwar
- Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hyung Sik Kim
- School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon 16419, 2066, Seobu-ro, Korea
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14
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Alhalmi A, Beg S, Kohli K, Waris M, Singh T. Nanotechnology Based Approach for Hepatocellular Carcinoma Targeting. Curr Drug Targets 2021; 22:779-792. [PMID: 33302831 DOI: 10.2174/1389450121999201209194524] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 10/20/2020] [Accepted: 10/20/2020] [Indexed: 11/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is the primary liver cancer that has shown a high incidence and mortality rate worldwide among several types of cancers. A large variety of chemotherapeutic agents employed for the treatment have a limited success rate owing to their limited site-specific drug targeting ability. Thus, there is a demand to develop novel approaches for the treatment of HCC. With advancements in nanotechnology-based drug delivery approaches, the challenges of conventional chemotherapy have been continuously decreasing. Nanomedicines constituted of lipidic and polymeric composites provide a better platform for delivering and opening new pathways for HCC treatment. A score of nanocarriers such as surface-engineered liposomes, nanoparticles, nanotubes, micelles, quantum dots, etc., has been investigated in the treatment of HCC. These nanocarriers are considered to be highly effective clinically for delivering chemotherapeutic drugs with high site-specificity ability and therapeutic efficiency. The present review highlights the current focus on the application of nanocarrier systems using various ligand-based receptor-specific targeting strategies for the treatment and management of HCC. Moreover, the article has also included information on the current clinically approved drug therapy for hepatocellular carcinoma treatment and updates of regulatory requirements for approval of such nanomedicines.
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Affiliation(s)
- Abdulsalam Alhalmi
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Sarwar Beg
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Kanchan Kohli
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Md Waris
- Department of Botany, Thakur Prasad Singh College, Patna, Magadh University, Bodh Gaya, India
| | - Tanuja Singh
- University Department of Botany, Patliputra University, Patna, Bihar, India
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15
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Kong FH, Ye QF, Miao XY, Liu X, Huang SQ, Xiong L, Wen Y, Zhang ZJ. Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma. Theranostics 2021; 11:5464-5490. [PMID: 33859758 PMCID: PMC8039945 DOI: 10.7150/thno.54822] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. Sorafenib is an oral kinase inhibitor that inhibits tumor cell proliferation and angiogenesis and induces cancer cell apoptosis. It also improves the survival rates of patients with advanced liver cancer. However, due to its poor solubility, fast metabolism, and low bioavailability, clinical applications of sorafenib have been substantially restricted. In recent years, various studies have been conducted on the use of nanoparticles to improve drug targeting and therapeutic efficacy in HCC. Moreover, nanoparticles have been extensively explored to improve the therapeutic efficacy of sorafenib, and a variety of nanoparticles, such as polymer, lipid, silica, and metal nanoparticles, have been developed for treating liver cancer. All these new technologies have improved the targeted treatment of HCC by sorafenib and promoted nanomedicines as treatments for HCC. This review provides an overview of hot topics in tumor nanoscience and the latest status of treatments for HCC. It further introduces the current research status of nanoparticle drug delivery systems for treatment of HCC with sorafenib.
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Affiliation(s)
- Fan-Hua Kong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Hepatobiliary Diseases of Wuhan University, Transplant Centre of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China
| | - Qi-Fa Ye
- Institute of Hepatobiliary Diseases of Wuhan University, Transplant Centre of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China
| | - Xiong-Ying Miao
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xi Liu
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Si-Qi Huang
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Xiong
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yu Wen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zi-Jian Zhang
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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16
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Ju J, Song YN, Wang K. Mechanism of Ferroptosis: A Potential Target for Cardiovascular Diseases Treatment. Aging Dis 2021; 12:261-276. [PMID: 33532140 PMCID: PMC7801281 DOI: 10.14336/ad.2020.0323] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Accepted: 03/23/2020] [Indexed: 01/08/2023] Open
Abstract
Ferroptosis is a form of programmed cell death caused by production of reactive oxygen species and disequilibrium of iron homeostasis. Many chemical compounds and clinical drugs induce ferroptosis in normal and cancer cells, while peroxidation inhibitors, iron chelators, and antioxidants can block ferroptosis. Glutathione peroxidase 4, ferroptosis suppressor protein 1, nuclear factor erythroid 2-related factor 2, and system Xc- are the negative regulators of ferroptosis, whereas nicotinamide adenine dinucleotide phosphate oxidase, p53, mitochondria voltage-dependent anion channel, and cysteinyl-tRNA synthetase function as positive regulators. Ferroptosis plays important roles in pathogen infection and tumor immunology. Recent studies suggest that ferroptosis plays a vital role in the pathogenesis of cardiovascular diseases (CVDs), which seriously threaten human health. Potential therapies designed around ferroptosis may alter the pathological progression of CVDs. Therefore, we redacted an overview of the discovery of ferroptosis, its regulatory mechanisms, and its potential impact on CVDs treatment.
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Affiliation(s)
- Jie Ju
- 1Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, China
| | - Ya-Nan Song
- 2Medical College of Qingdao University, Qingdao, China
| | - Kun Wang
- 1Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, China
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17
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Novel multi-targeted nanoparticles for targeted co-delivery of nucleic acid and chemotherapeutic agents to breast cancer tissues. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 118:111494. [DOI: 10.1016/j.msec.2020.111494] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 08/12/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
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18
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Recent advances of sorafenib nanoformulations for cancer therapy: Smart nanosystem and combination therapy. Asian J Pharm Sci 2020; 16:318-336. [PMID: 34276821 PMCID: PMC8261086 DOI: 10.1016/j.ajps.2020.07.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 07/01/2020] [Accepted: 07/25/2020] [Indexed: 12/21/2022] Open
Abstract
Sorafenib, a molecular targeted multi-kinase inhibitor, has received considerable interests in recent years due to its significant profiles of efficacy in cancer therapy. However, poor pharmacokinetic properties such as limited water solubility, rapid elimination and metabolism lead to low bioavailability, restricting its further clinical application. Over the past decade, with substantial progress achieved in the development of nanotechnology, various types of smart sorafenib nanoformulations have been developed to improve the targetability as well as the bioavailability of sorafenib. In this review, we summarize various aspects from the preparation and characterization to the evaluation of antitumor efficacy of numerous stimuli-responsive sorafenib nanodelivery systems, particularly with emphasis on their mechanism of drug release and tumor microenvironment response. In addition, this review makes great effort to summarize the nanosystem-based combination therapy of sorafenib with other antitumor agents, which can provide detailed information for further synergistic cancer therapy. In the final section of this review, we also provide a detailed discussion of future challenges and prospects of designing and developing ideal sorafenib nanoformulations for clinical cancer therapy.
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Younis MA, Khalil IA, Harashima H. Gene Therapy for Hepatocellular Carcinoma: Highlighting the Journey from Theory to Clinical Applications. ADVANCED THERAPEUTICS 2020. [DOI: 10.1002/adtp.202000087] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Mahmoud A. Younis
- Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences Hokkaido University Kita‐12, Nishi‐6, Kita‐ku Sapporo 060‐0812 Japan
- Faculty of Pharmacy Assiut University Assiut 71526 Egypt
| | - Ikramy A. Khalil
- Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences Hokkaido University Kita‐12, Nishi‐6, Kita‐ku Sapporo 060‐0812 Japan
- Faculty of Pharmacy Assiut University Assiut 71526 Egypt
| | - Hideyoshi Harashima
- Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences Hokkaido University Kita‐12, Nishi‐6, Kita‐ku Sapporo 060‐0812 Japan
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20
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Lin X, Ping J, Wen Y, Wu Y. The Mechanism of Ferroptosis and Applications in Tumor Treatment. Front Pharmacol 2020; 11:1061. [PMID: 32774303 PMCID: PMC7388725 DOI: 10.3389/fphar.2020.01061] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 06/30/2020] [Indexed: 01/17/2023] Open
Abstract
Iron-dependent ferroptosis is a new form of cell death in recent years, which is driven by lipid peroxidation. The lethal lipid accumulation caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of the ferroptosis process. In recent years, with the in-depth study of ferroptosis, various types of diseases have been reported to be related to ferroptosis. In other words, ferroptosis, which has attracted widespread attention in the fields of biochemistry, oncology, and especially materials science, can undoubtedly provide a new way for patients. This review introduces the relevant mechanisms of ferroptosis, the relationship between ferroptosis and various cancers, as well as the application of ferroptosis in tumor treatment. We also sorted out the genes and drugs that regulate ferroptosis. Moreover, small molecule compound-induced ferroptosis has a strong inhibitory effect on tumor growth in a drug-resistant environment, which can enhance the sensitivity of chemotherapeutic drugs, suggesting that ferroptosis is very important in the treatment of tumor drug resistance, but the details are still unclear. How to use ferroptosis to fight cancer, and how to prevent drug-resistant tumor cells have become the focus and direction of research. At the end of the article, some existing problems related to ferroptosis are summarized for future research.
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Affiliation(s)
- Xinyue Lin
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jieyi Ping
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yi Wen
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yan Wu
- School of Medicine, Jiangsu University, Zhenjiang, China.,Gynecology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
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21
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Sepand MR, Ranjbar S, Kempson IM, Akbariani M, Muganda WCA, Müller M, Ghahremani MH, Raoufi M. Targeting non-apoptotic cell death in cancer treatment by nanomaterials: Recent advances and future outlook. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2020; 29:102243. [PMID: 32623018 DOI: 10.1016/j.nano.2020.102243] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 04/29/2020] [Accepted: 06/08/2020] [Indexed: 12/19/2022]
Abstract
Many tumors develop resistance to most of the apoptosis-based cancer therapies. In this sense targeting non-apoptotic forms of cell death including necroptosis, autophagy and ferroptosis may have therapeutic benefits in apoptosis-defective cancer cells. Nanomaterials have shown great advantages in cancer treatment owing to their unique characteristics. Besides, the capability of nanomaterials to induce different forms of cell death has gained widespread attention in cancer treatment. Reports in this field reflect the therapeutic potential of necroptotic cell death induced by nanomaterials in cancer. Also, autophagic cell death induced by nanomaterials alone and as a part of chemo-, radio- and photothermal therapy holds great promise as anticancer therapeutic option. Besides, ferroptosis induction by iron-based nanomaterials in drug delivery, immunotherapy, hyperthermia and imaging systems shows promising results in malignancies. Hence, this review is devoted to the latest efforts and the challenges in this field of research and its clinical merits.
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Affiliation(s)
- Mohammad Reza Sepand
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Sheyda Ranjbar
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Ivan M Kempson
- Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia; School of Pharmacy and Medical Sciences, University of South Australia, SA, Australia
| | - Mostafa Akbariani
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mareike Müller
- Physical Chemistry I and Research Center of Micro and Nanochemistry (Cμ), University of Siegen, Siegen, Germany
| | - Mohammad Hossein Ghahremani
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Raoufi
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Physical Chemistry I and Research Center of Micro and Nanochemistry (Cμ), University of Siegen, Siegen, Germany.
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22
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Calderan L, Malatesta M. Imaging techniques in nanomedical research. Eur J Histochem 2020; 64. [PMID: 32613820 PMCID: PMC7341075 DOI: 10.4081/ejh.2020.3151] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 06/22/2020] [Indexed: 12/20/2022] Open
Abstract
About twenty years ago, nanotechnology began to be applied to biomedical issues giving rise to the research field called nanomedicine. Thus, the study of the interactions between nanomaterials and the biological environment became of primary importance in order to design safe and effective nanoconstructs suitable for diagnostic and/or therapeutic purposes. Consequently, imaging techniques have increasingly been used in the production, characterisation and preclinical/clinical application of nanomedical tools. This work aims at making an overview of the microscopy and imaging techniques in vivo and in vitro in their application to nanomedical investigation, and to stress their contribution to this developing research field.
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Affiliation(s)
- Laura Calderan
- Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona.
| | - Manuela Malatesta
- Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona.
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23
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Ruman U, Fakurazi S, Masarudin MJ, Hussein MZ. Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities. Int J Nanomedicine 2020; 15:1437-1456. [PMID: 32184597 PMCID: PMC7060777 DOI: 10.2147/ijn.s236927] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 02/18/2020] [Indexed: 12/13/2022] Open
Abstract
The development of therapeutics and theranostic nanodrug delivery systems have posed a challenging task for the current researchers due to the requirement of having various nanocarriers and active agents for better therapy, imaging, and controlled release of drugs efficiently in one platform. The conventional liver cancer chemotherapy has many negative effects such as multiple drug resistance (MDR), high clearance rate, severe side effects, unwanted drug distribution to the specific site of liver cancer and low concentration of drug that finally reaches liver cancer cells. Therefore, it is necessary to develop novel strategies and novel nanocarriers that will carry the drug molecules specific to the affected cancerous hepatocytes in an adequate amount and duration within the therapeutic window. Therapeutics and theranostic systems have advantages over conventional chemotherapy due to the high efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimum side effects. These nanocarriers possess high drug accumulation in the tumor area while minimizing toxic effects on healthy tissues. This review focuses on the current research on nanocarrier-based therapeutics and theranostic drug delivery systems excluding the negative consequences of nanotechnology in the field of drug delivery systems. However, clinical developments of theranostics nanocarriers for liver cancer are considered outside of the scope of this article. This review discusses only the recent developments of nanocarrier-based drug delivery systems for liver cancer therapy and diagnosis. The negative consequences of individual nanocarrier in the drug delivery system will also not be covered in this review.
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Affiliation(s)
- Umme Ruman
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Sharida Fakurazi
- Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience Universiti, Putra43400, Malaysia
- Department of Human Anatomy, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Mas Jaffri Masarudin
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
- Laboratory of Vaccine and Immunotherapeutics, Institute of Bioscience Universiti, Putra43400, Malaysia
- Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Mohd Zobir Hussein
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
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24
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Poojari R, Sawant AV, Kini S, Srivastava R, Panda D. Antihepatoma activity of multifunctional polymeric nanoparticles via inhibition of microtubules and tyrosine kinases. Nanomedicine (Lond) 2020; 15:381-396. [PMID: 31990235 DOI: 10.2217/nnm-2019-0349] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 12/10/2019] [Indexed: 12/19/2022] Open
Abstract
Aim: Synthesis of poly-L-lactic acid nanoparticles comprising of microtubule-inhibitor docetaxel and tyrosine kinase inhibitor sorafenib (PLDS NPs) for hepatoma treatment. Materials & methods: PLDS NPs were prepared by the emulsion solvent evaporation method and the anticancer activity was evaluated in Huh7 hepatoma cells. Results: Real-time imaging of quantum dots incorporating poly-L-lactic acid nanoparticles showed a rapid internalization of the nanoparticles in Huh7 cells. PLDS NPs exerted stronger antiproliferative, apoptotic and antiangiogenic effects than free single drug counterparts. They strongly promoted microtubule bundling, multinucleation and increased mitotic index in Huh7 cells. They also inhibited the expression of pERK1/2, pAKT and cyclin D1. Conclusion: We developed a single-nanoscale platform for dual drug delivery and high-sensitivity quantum dots imaging for hepatoma treatment. [Formula: see text].
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Affiliation(s)
- Radhika Poojari
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India
| | - Avishkar V Sawant
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India
| | - Sudarshan Kini
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India
- Nitte University Centre for Science Education & Research, Nitte (Deemed to be University), Paneer Campus, Deralakatte, Mangaluru, 575018, India
| | - Rohit Srivastava
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India
| | - Dulal Panda
- Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India
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25
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Clavreul A, Roger E, Pourbaghi-Masouleh M, Lemaire L, Tétaud C, Menei P. Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma. Drug Deliv 2019; 25:1756-1765. [PMID: 30338715 PMCID: PMC6225440 DOI: 10.1080/10717544.2018.1507061] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (>90%), and a drug payload of 2.11 ± 0.03 mg/g of LNC dispersion. They inhibited in vitro angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. In vivo studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potential of LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.
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Affiliation(s)
- Anne Clavreul
- a Département de Neurochirurgie , CHU , Angers , France.,b CRCINA, INSERM , Université de Nantes, Université d'Angers , Angers , France
| | - Emilie Roger
- c MINT, INSERM 1066, CNRS 6021 , Université d'Angers, UNIV Angers , Angers , France
| | - Milad Pourbaghi-Masouleh
- b CRCINA, INSERM , Université de Nantes, Université d'Angers , Angers , France.,d Division of Drug Delivery and Tissue Engineering, School of Pharmacy , University of Nottingham , Nottingham , UK
| | - Laurent Lemaire
- c MINT, INSERM 1066, CNRS 6021 , Université d'Angers, UNIV Angers , Angers , France.,e PRISM-IRM , UNIV Angers , Angers , France
| | - Clément Tétaud
- b CRCINA, INSERM , Université de Nantes, Université d'Angers , Angers , France
| | - Philippe Menei
- a Département de Neurochirurgie , CHU , Angers , France.,b CRCINA, INSERM , Université de Nantes, Université d'Angers , Angers , France
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26
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Wang H, Sun S, Zhang Y, Wang J, Zhang S, Yao X, Chen L, Gao Z, Xie B. Improved drug targeting to liver tumor by sorafenib-loaded folate-decorated bovine serum albumin nanoparticles. Drug Deliv 2019; 26:89-97. [PMID: 30744448 PMCID: PMC6374969 DOI: 10.1080/10717544.2018.1561766] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background: To prepare sorafenib-loaded folate-decorated bovine serum nanoparticles (FA-SRF-BSANPs) and investigate their effect on the tumor targeting. Methods: The nanoparticles were characterized and evaluated by in vivo and in vitro experiments. Results: SRF-loaded BSA nanoparticles (SRF-BSANPs) was first prepared and modified with folic acid by chemical coupling to obtain FA-SRF-BSANPs. The average particle size, zeta potential, entrapment efficiency, and drug loading of the optimized FA-SRF-BSANPs were 158.00 nm, −16.27 mV, 77.25%, and 7.73%, respectively. The stability test showed that FA-SRF-BSANPs remained stable for more than 1 month at room temperature. The TEM analysis showed that the surface of FA-SRF-BSANPs was nearly spherical. XRD analysis showed that the drug existed in. the nanoparticles in an amorphous state. FA-SRF-BSANPs can promote the intracellular uptake of hepatoma cells (SMMC-7721) with the strongest inhibitory effect compared with SRF-BSANPs and sorafenib solution. Furthermore, the tumor targeting of FA-SRF-BSANPs (Ctumor/Cblood, 0.666 ± 0.053) was significantly higher than those of SRF-BSANPs (Ctumor/Cblood, 0.560 ± 0.083) and sorafenib-solution (Ctumor/Cblood, 0.410 ± 0.038) in nude mice with liver cancer. Conclusion: FA-modified albumin nanoparticles are good carriers for delivering SRF to the tumor tissue, which can improve the therapeutic effect and reduce the side effects of the drug.
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Affiliation(s)
- Haipeng Wang
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Shuilin Sun
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Yu Zhang
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Jiayi Wang
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Shouhua Zhang
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Xuebing Yao
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Ling Chen
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Zhen Gao
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
| | - Baogang Xie
- a Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, School of Pharmaceutical Science , Nanchang University , Nanchang PR China
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Xu X, Tang X, Wu X, Feng X. Biosynthesis of sorafenib coated graphene nanosheets for the treatment of gastric cancer in patients in nursing care. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2018; 191:1-5. [PMID: 30557787 DOI: 10.1016/j.jphotobiol.2018.11.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 11/18/2018] [Accepted: 11/19/2018] [Indexed: 12/31/2022]
Abstract
Sorafenib (SRF) is a well-known tyrosine kinase inhibiting anticancer drug which iseffectual against multiple carcinomas especially gastric cancers by targeting the Ras/Raf/Mek/Erk cascade pathway and blocking the tumor cell proliferation. In the present work, we have reduced graphene oxide (GO) in presence of sorafenib using ascorbic as green reducing agent for the treatment of gastric cancers. Sorafenib reduced graphene oxide (SRGO) were obtained with a transparent and smoothmorphology. The drug loaded SRGO has presented significant cytotoxic effect against SGC7901 cancer cells when compared to that of the free SRF and blank NPs in the equivalent concentrations. Additionally, from the Hoechst 33382 staining study it was evident that the cells in untreated groups remained intact with its round shape and intact nuclei while the SRGO treated cells have shown a cell transformation with apoptosis of gastric cancer cell lines. Based on these results, we can conclude that SRGO might extend an enormous prospective in the treatment of gastric cancers.
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Affiliation(s)
- Xiaoyue Xu
- The Third Department of Tumor Surgery, Tangshan Gongren Hospital, People's Republic of China
| | - Xiaoyu Tang
- Department of Rehabilitation Medicine, Tangshan Gongren Hospital, People's Republic of China
| | - Xiaoxu Wu
- The Department of Radiology, Tangshan Gongren Hospital, People's Republic of China
| | - Xiufang Feng
- The Third Department of Tumor Surgery, Tangshan Gongren Hospital, People's Republic of China.
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28
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Wang S, Luo J, Zhang Z, Dong D, Shen Y, Fang Y, Hu L, Liu M, Dai C, Peng S, Fang Z, Shang P. Iron and magnetic: new research direction of the ferroptosis-based cancer therapy. Am J Cancer Res 2018; 8:1933-1946. [PMID: 30416846 PMCID: PMC6220147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 09/17/2018] [Indexed: 06/09/2023] Open
Abstract
Ferroptosis is an iron depend cell death which caused by lipid peroxidation. Abnormal iron metabolism and high intracellular iron content are the characteristics of most cancer cells. Iron is a promoter of cell growth and proliferation. However, iron also could take part in Fenton reaction to produce reactive oxygen species (ROS). The intercellular ROS could induce lipid peroxidation, which is necessary for ferroptosis. Iron metabolism mainly includes three parts: iron uptake, storage and efflux. Therefore, iron metabolism-related genes could regulate intercellular iron content and status, which can be involved ferroptosis. In recent years, the application of nanoparticles in cancer therapy research has become more and more extensive. The iron-based nanoparticles (iron-based NPs) can release ferrous (Fe2+) or ferric (Fe3+) in acidic lysosomes and inducing ferroptosis. Magnetic field is widely used in the targeted concentration of iron-based NPs related disease therapy. Furthermore, multiple studies showed that magnetic fields can inhibit cancer cell proliferation by promoting intracellular ROS production. Herein, we focus on the relationship of between ferroptosis and iron metabolism in cancer cells, the application of nanoparticles and magnetic field in inducing ferroptosis of cancer cells, and trying to provide new ideas for cancer treatment research.
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Affiliation(s)
- Shenghang Wang
- School of Life Sciences, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
| | - Jie Luo
- School of Life Sciences, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
| | - Zhihao Zhang
- School of Life Sciences, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
| | - Dandan Dong
- School of Life Sciences, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
| | - Ying Shen
- School of Life Sciences, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
| | - Yanwen Fang
- Zhejiang Heye Health Technology Co., Ltd.Anji, China
| | - Lijiang Hu
- Zhejiang Heye Health Technology Co., Ltd.Anji, China
| | - Mengyu Liu
- Zhejiang Heye Health Technology Co., Ltd.Anji, China
| | - Chengfu Dai
- Department of Spine Surgery, Shenzhen People’s HospitalShenzhen, China
| | - Songlin Peng
- Department of Spine Surgery, Shenzhen People’s HospitalShenzhen, China
| | - Zhicai Fang
- Zhejiang Heye Health Technology Co., Ltd.Anji, China
| | - Peng Shang
- Institute for Research & Development in Shenzhen, Northwestern Polytechnical UniversityShenzhen 518057, China
- Key Laboratory for Space Biosciences and Biotechnology, Northwestern Polytechnical UniversityXi’an 710072, Shaanxi, China
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29
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Anwar DM, Khattab SN, Helmy MW, Kamal MK, Bekhit AA, Elkhodairy KA, Elzoghby AO. Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma. Bioconjug Chem 2018; 29:3026-3041. [PMID: 30110148 DOI: 10.1021/acs.bioconjchem.8b00428] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In this study, promising approaches of dual-targeted micelles and drug-polymer conjugation were combined to enable injection of poorly soluble anticancer drugs together with site-specific drug release. Ursodeoxycholic acid (UDCA) as a hepatoprotective agent was grafted to maltodextrin (MD) via carbodiimide coupling to develop amphiphilic maltodextrin-ursodeoxycholic acid (MDCA)-based micelles. Sulfasalazine (SSZ), as a novel anticancer agent, was conjugated via a tumor-cleavable ester bond to MD backbone to obtain tumor-specific release, whereas resveratrol (RSV) was physically entrapped within the hydrophobic micellar core. For maximal tumor-targeting, both folic acid (FA) and lactobionic acid (LA) were coupled to the surface of micelles to obtain dual-targeted micelles. The decrease of critical micelle concentration (CMC) from 0.012 to 0.006 mg/mL declares the significance of a dual hydrophobicized core of micelles by both UDCA and SSZ. The dual-targeted micelles showed a great hemocompatibility, as well as enhanced cytotoxicity and internalization into HepG-2 liver cancer cells via binding to overexpressed folate and asialoglycoprotein receptors. In vivo, the micelles demonstrated superior antitumor effects revealed as reduction in the liver/body weight ratio, inhibition of angiogenesis, and enhanced apoptosis. Overall, combined strategies of dual active targeted micelles with bioresponsive drug conjugation could be utilized as a promising approach for tumor-targeted drug delivery.
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Affiliation(s)
| | - Sherine N Khattab
- Department of Chemistry and #Department of Oceanography , Faculty of Science, Alexandria University , Alexandria 21321 , Egypt
| | - Maged W Helmy
- Department of Pharmacology and Toxicology , Faculty of Pharmacy, Damanhour University , Damanhour 22516 , Egypt
| | - Mohamed K Kamal
- Department of Toxicology , Central Laboratories of Alexandria, Health Affairs Directorate , Alexandria 21518 , Egypt
| | - Adnan A Bekhit
- Pharmacy Program, Allied Health Department, College of Health Sciences , University of Bahrain , P.O. Box 32038, Zallaq , Kingdom of Bahrain
| | | | - Ahmed O Elzoghby
- Division of Engineering in Medicine, Department of Medicine , Brigham and Women's Hospital, Harvard Medical School , Boston , Massachusetts 02115.,Harvard-MIT Division of Health Sciences and Technology, Cambridge , Massachusetts 02139
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30
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Khan MA, Raza A, Ovais M, Sohail MF, Ali S. Current state and prospects of nano-delivery systems for sorafenib. INT J POLYM MATER PO 2018. [DOI: 10.1080/00914037.2018.1429434] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Muhammad Adeeb Khan
- School of Material Science and Engineering (MSE), Nanyang Technological University, Nanyang, Singapore
- Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan
- NILOP Nanomedicine Research Labs, National Institute of Lasers & Optronics (NILOP), Islamabad, Pakistan
| | - Abida Raza
- NILOP Nanomedicine Research Labs, National Institute of Lasers & Optronics (NILOP), Islamabad, Pakistan
| | - Muhammad Ovais
- Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Farhan Sohail
- Department of Medicine, Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
- Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore Campus, Lahore, Pakistan
| | - Shaukat Ali
- Department of Zoology, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan
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31
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Turato C, Balasso A, Carloni V, Tiribelli C, Mastrotto F, Mazzocca A, Pontisso P. New molecular targets for functionalized nanosized drug delivery systems in personalized therapy for hepatocellular carcinoma. J Control Release 2017; 268:184-197. [PMID: 29051062 DOI: 10.1016/j.jconrel.2017.10.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 10/12/2017] [Accepted: 10/14/2017] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma, the most frequent solid tumor of the liver, has a very poor prognosis, being the second most common cause of death from cancer worldwide. The incidence and mortality of this liver tumor are increasing in most areas of the world as a consequence of aging and the emerging of new risk factors such as the metabolic syndrome, beside the recognized role of hepatitis B and C viral infections and alcohol abuse. Despite the increasing knowledge on the molecular mechanisms underlying hepatic carcinogenesis, effective therapeutic strategies are still an unmet clinical need. Efforts have been made to develop selective drugs as well as effective targeted drug delivery systems. The development of novel drug carriers for therapeutic molecules can indeed offer a valuable strategy to ameliorate the efficacy of HCC treatment. In this review, we discuss recent drug delivery strategies for HCC treatment based on the exploitation of targeted nanoparticles (NPs). Indeed, a few of these platforms have achieved an advanced stage of preclinical development. Here, we review the most promising drug nanovehicles based on both synthetic and natural polymers, including polysaccharides that have emerged for their biocompatibility and biodegradability. To maximize site-selectivity and therapeutic efficacy, drug delivery systems should be functionalized with ligands which can specifically recognize and bind targets expressed by HCC, namely cell membrane associated antigens, receptors or biotransporters. Cell surface and intracellular molecular targets are exploited either to selectively deliver drug-loaded nanovehicles or to design novel selective therapeutics. In conclusion, the combination of novel and safe drug delivery strategies based on site-specific targeted drug nanovehicles with therapeutic molecular targets may significantly improve the pharmacological efficacy for the treatment of HCC.
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Affiliation(s)
| | - Anna Balasso
- Department of Pharmaceutical & Pharmacological Sciences, University of Padova, Padova, Italy
| | - Vinicio Carloni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | | | - Francesca Mastrotto
- Department of Pharmaceutical & Pharmacological Sciences, University of Padova, Padova, Italy
| | - Antonio Mazzocca
- Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.
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32
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Li DL, Tan JE, Tian Y, Huang S, Sun PH, Wang M, Han YJ, Li HS, Wu HB, Zhang XM, Xu YK, Wang QS. Multifunctional superparamagnetic nanoparticles conjugated with fluorescein-labeled designed ankyrin repeat protein as an efficient HER2-targeted probe in breast cancer. Biomaterials 2017; 147:86-98. [PMID: 28938164 DOI: 10.1016/j.biomaterials.2017.09.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 08/13/2017] [Accepted: 09/07/2017] [Indexed: 12/14/2022]
Abstract
Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging. Our results showed that SPIO-G3-5MF nanoparticles, which possessed uniform size of about 100 nm, favorable dispersity and low cytotoxicity, could selectively bind to HER2-positive breast cancer cells even in the presence of trastuzumab. Biodistribution assay demonstrated that abundant accumulation and long retention of SPIO-G3-5MF were observed in HER2-positive transplantation breast tumors although a portion of SPIO-G3-5MF nanoparticles were unavoidably captured by liver and spleen. Further MR imaging revealed that SPIO-G3-5MF could selectively image HER2-positive transplantation breast tumors, yielding remarkable T2 signal reduction (50.33 ± 2.90% at 6 h and 47.29 ± 9.36% at 24 h). Our study suggested that SPIO-G3-5MF might be a promising MR molecular probe for diagnosing and monitoring HER2 expression state of breast cancer in the future.
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Affiliation(s)
- Dong-Li Li
- Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Jian-Er Tan
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Ying Tian
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Shun Huang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Peng-Hui Sun
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Meng Wang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yan-Jiang Han
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Hong-Sheng Li
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Hu-Bing Wu
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Xing-Mei Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yi-Kai Xu
- Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Quan-Shi Wang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
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33
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Jiang Y, Liu S, Zhang Y, Li H, He H, Dai J, Jiang T, Ji W, Geng D, Elzatahry AA, Alghamdi A, Fu D, Deng Y, Zhao D. Magnetic mesoporous nanospheres anchored with LyP-1 as an efficient pancreatic cancer probe. Biomaterials 2017; 115:9-18. [PMID: 27871003 DOI: 10.1016/j.biomaterials.2016.11.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 10/10/2016] [Accepted: 11/07/2016] [Indexed: 01/17/2023]
Abstract
Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging. After systematic administration, these LyP-1 immobilized nanospheres are found to actively target to mouse orthotopic xenograft of pancreatic cancer, which opens up the door for applications in early probing and diagnosis of pancreatic cancer by the multimodal imaging.
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Affiliation(s)
- Yongjian Jiang
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Shaojun Liu
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yu Zhang
- Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200433, China
| | - Hengchao Li
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Hang He
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Juntao Dai
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Tao Jiang
- Department of Radiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
| | - Weihang Ji
- Institute for Complex Engineered Systems, Carnegie Mellon University, Pittsburgh, PA 15213, USA
| | - Daoying Geng
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Ahmed A Elzatahry
- Materials Science and Technology Program, College of Arts and Sciences, Qatar University, Doha 2713, Qatar
| | - Abdulaziz Alghamdi
- Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Deliang Fu
- Department of Pancreatic Surgery, Nephrology & Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
| | - Yonghui Deng
- Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200433, China; State Key Lab of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.
| | - Dongyuan Zhao
- Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200433, China
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34
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Poojari R, Kini S, Srivastava R, Panda D. Intracellular interactions of electrostatically mediated layer-by-layer assembled polyelectrolytes based sorafenib nanoparticles in oral cancer cells. Colloids Surf B Biointerfaces 2016; 143:131-138. [PMID: 26998875 DOI: 10.1016/j.colsurfb.2016.03.024] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Revised: 03/07/2016] [Accepted: 03/08/2016] [Indexed: 12/22/2022]
Abstract
In this paper, we report the preparation of LbL-nanoSraf (100-300nm) comprising of layer-by-layer (LbL) assembled polyelectrolytes dextran-sulfate/poly-l-arginine, with a multikinase inhibitor sorafenib (Sraf) encapsulated calcium carbonate (CaCO3) nanoparticles for oral cancer therapy in vitro. The zeta potential of LbL-nanoSraf exhibited a negative charge of the polyanionic dextran sulfate, which alternated with a positive charge of polycationic poly-l-arginine indicating a successful LbL assembly of the two polyelectrolyte bilayers on the CaCO3 nanoparticles. The LbL-nanoSraf exhibited an encapsulation efficiency of 61±4%. The LbL-nanoSraf was characterized using field-emission gun scanning electron microscopy, X-ray powder diffraction, atomic force microscopy and confocal laser scanning microscopy. Confocal laser scanning microscopy, flow cytometry and transmission electron microscopic investigations showed the internalization of LbL-nanoSraf in human oral cancer (KB) cells. The LbL-nanoSraf exhibited more potent antiproliferative, apoptotic and antimigratory activities in KB cells than the free drug Sraf. The findings could promote the application of nano-sized LbL assembled polyelectrolytes for the delivery of Raf-kinase inhibitors and provide mechanistic insights for oral cancer therapy.
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Affiliation(s)
- Radhika Poojari
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
| | - Sudarshan Kini
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Rohit Srivastava
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India
| | - Dulal Panda
- Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
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35
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Cheng HT, Hsieh SY, Chen TH, Hung PF, Pan SH. WITHDRAWN: Sorafenib-fortified Zein-Chondroitin Sulphate Biopolymer Nanoparticles as a Novel Therapeutic System in Gastric Cancers Treatment. Carbohydr Polym 2016. [DOI: 10.1016/j.carbpol.2016.06.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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36
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Kheiri Manjili H, Ma’mani L, Tavaddod S, Mashhadikhan M, Shafiee A, Naderi-Manesh H. D, L-Sulforaphane Loaded Fe3O4@ Gold Core Shell Nanoparticles: A Potential Sulforaphane Delivery System. PLoS One 2016; 11:e0151344. [PMID: 26982588 PMCID: PMC4794166 DOI: 10.1371/journal.pone.0151344] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2015] [Accepted: 02/08/2016] [Indexed: 11/19/2022] Open
Abstract
A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-xL), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-xL genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells.
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Affiliation(s)
- Hamidreza Kheiri Manjili
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Leila Ma’mani
- Department of Nanotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
| | - Sharareh Tavaddod
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Maedeh Mashhadikhan
- Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Shafiee
- Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran
| | - Hossein Naderi-Manesh
- Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
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37
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Suarasan S, Simon T, Boca S, Tomuleasa C, Astilean S. Gelatin-coated Gold Nanoparticles as Carriers of FLT3 Inhibitors for Acute Myeloid Leukemia Treatment. Chem Biol Drug Des 2016; 87:927-35. [PMID: 26808072 DOI: 10.1111/cbdd.12725] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2015] [Revised: 10/30/2015] [Accepted: 01/16/2016] [Indexed: 12/11/2022]
Abstract
This study presents the design of a gold nanoparticle (AuNPs)-drug system with improved efficiency for the treatment of acute myeloid leukemia. The system is based on four different FLT3 inhibitors, namely midostaurin, sorafenib, lestaurtinib, and quizartinib, which were independently loaded onto gelatin-coated gold nanoparticles. Detailed investigation of the physicochemical properties of the formed complexes lead to the selection of quizartinib-loaded AuNPs for the in vitro evaluation of the biological effects of the formed complex against OCI-AML3 acute myeloid leukemia cells. Viability tests by MTT demonstrated that the proposed drug complex has improved efficacy when compared with the drug alone. The obtained results constitute a premise for further in vivo investigation of such drug vehicles based on AuNPs. To the best of our knowledge, this is the first study that investigates the delivery of the above-mentioned FLT3 inhibitors via gelatin-coated gold nanoparticles.
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Affiliation(s)
- Sorina Suarasan
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, T. Laurian 42, 400271, Cluj-Napoca, Romania.,Faculty of Physics, Babes-Bolyai University, M. Kogalniceanu, 40084
| | - Timea Simon
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, T. Laurian 42, 400271, Cluj-Napoca, Romania.,Faculty of Physics, Babes-Bolyai University, M. Kogalniceanu, 40084
| | - Sanda Boca
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, T. Laurian 42, 400271, Cluj-Napoca, Romania.,Faculty of Physics, Babes-Bolyai University, M. Kogalniceanu, 40084
| | - Ciprian Tomuleasa
- Department of Hematology, Ion Chiricuta Oncology Institute, Bulevardul 21 Decembrie 1918 Nr 73, 400124, Cluj-Napoca, Romania.,Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, G. Marinescu 23, 400337, Cluj-Napoca, Romania
| | - Simion Astilean
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, T. Laurian 42, 400271, Cluj-Napoca, Romania.,Faculty of Physics, Babes-Bolyai University, M. Kogalniceanu, 40084
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38
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Cheng HT, Hsieh SY, Chen TH, Hung PF, Pan SH. Sorafenib-fortified zein–chondroitin sulphate biopolymer nanoparticles as a novel therapeutic system in gastric cancer treatment. RSC Adv 2016. [DOI: 10.1039/c6ra06775a] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Gastric cancer is the second most common cause of cancer related death worldwide and lacks a highly effective treatment for the advanced disease.
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Affiliation(s)
- Hao-Tsai Cheng
- Division of Gastroenterology
- Department of Internal Medicine
- Linkou Chang Gung Memorial Hospital
- Chang Gung University College of Medicine
- Taoyuan
| | - Sen-Yung Hsieh
- Department of Gastroenterology and Hepatology
- Chang Gung Memorial Hospital
- Chang Gung University College of Medicine
- Taoyuan
- Taiwan
| | - Tsung-Hsing Chen
- Division of Gastroenterology
- Department of Internal Medicine
- Linkou Chang Gung Memorial Hospital
- Chang Gung University College of Medicine
- Taoyuan
| | - Pei-Fang Hung
- Department of Internal Medicine
- College of Medicine
- National Taiwan University
- Taiwan
| | - Szu-Hua Pan
- Graduate Institute of Medical Genomics and Proteomics
- College of Medicine
- National Taiwan University
- Taipei 100
- Taiwan
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39
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Varshosaz J, Farzan M. Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma. World J Gastroenterol 2015; 21:12022-12041. [PMID: 26576089 PMCID: PMC4641122 DOI: 10.3748/wjg.v21.i42.12022] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/31/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorable systemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs (siRNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and siRNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited side-effects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is over-expressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and non-viral siRNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic siRNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and siRNA-based therapeutics in HCC and discussed in detail in this article.
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Grillone A, Riva ER, Mondini A, Forte C, Calucci L, Innocenti C, de Julian Fernandez C, Cappello V, Gemmi M, Moscato S, Ronca F, Sacco R, Mattoli V, Ciofani G. Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles. Adv Healthc Mater 2015; 4:1681-90. [PMID: 26039933 DOI: 10.1002/adhm.201500235] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/13/2015] [Indexed: 01/02/2023]
Abstract
Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging.
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Affiliation(s)
- Agostina Grillone
- Istituto Italiano di Tecnologia; Center for Micro-BioRobotics @SSSA; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
- Scuola Superiore Sant'Anna; The BioRobotics Institute; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
| | - Eugenio Redolfi Riva
- Istituto Italiano di Tecnologia; Center for Micro-BioRobotics @SSSA; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
- Scuola Superiore Sant'Anna; The BioRobotics Institute; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
| | - Alessio Mondini
- Istituto Italiano di Tecnologia; Center for Micro-BioRobotics @SSSA; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
| | - Claudia Forte
- Istituto di Chimica dei Composti OrganoMetallici; Consiglio Nazionale delle Ricerche - CNR; Via Giuseppe Moruzzi 1 56124 Pisa Italy
| | - Lucia Calucci
- Istituto di Chimica dei Composti OrganoMetallici; Consiglio Nazionale delle Ricerche - CNR; Via Giuseppe Moruzzi 1 56124 Pisa Italy
| | - Claudia Innocenti
- INSTM and Department of Chemistry “Ugo Shiff”; University of Florence; Via della Lastruccia 3-13 50019 Sesto Fiorentino Firenze Italy
| | - Cesar de Julian Fernandez
- Istituto dei Materiali per l'Elettronica e il Magnetismo; Consiglio Nazionale delle Ricerche - CNR; Parco Area delle Scienze 37/A 43124 Parma Italy
| | - Valentina Cappello
- Istituto Italiano di Tecnologia; Center for Nanotechnology Innovation @NEST; Piazza San Silvestro 12 56127 Pisa Italy
| | - Mauro Gemmi
- Istituto Italiano di Tecnologia; Center for Nanotechnology Innovation @NEST; Piazza San Silvestro 12 56127 Pisa Italy
| | - Stefania Moscato
- Dipartimento di Medicina Clinica e Sperimentale; Università di Pisa; Via Savi 10 56126 Pisa Italy
| | - Francesca Ronca
- Università di Pisa; Dipartimento di Patologia Chirurgica; Medica, Molecolare e dell'Area Critica; Via Savi 10 56126 Pisa Italy
| | - Rodolfo Sacco
- Unità Operativa di Gastroenterologia e Malattie del Ricambio; Azienda Ospedaliera-Universitaria Pisana; Via Paradisa 2 56124 Pisa Italy
| | - Virgilio Mattoli
- Istituto Italiano di Tecnologia; Center for Micro-BioRobotics @SSSA; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
| | - Gianni Ciofani
- Istituto Italiano di Tecnologia; Center for Micro-BioRobotics @SSSA; Viale Rinaldo Piaggio 34 56025 Pontedera Pisa Italy
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Wang L, An Y, Yuan C, Zhang H, Liang C, Ding F, Gao Q, Zhang D. GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells. Int J Nanomedicine 2015; 10:2507-19. [PMID: 25848268 PMCID: PMC4386779 DOI: 10.2147/ijn.s77642] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Methods Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. Results When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. Conclusion The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells.
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Affiliation(s)
- Ling Wang
- Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People's Republic of China
| | - Yanli An
- Medical School, Southeast University, Nanjing, People's Republic of China
| | - Chenyan Yuan
- Department of Clinical Laboratory, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People's Republic of China
| | - Hao Zhang
- Medical School, Southeast University, Nanjing, People's Republic of China
| | - Chen Liang
- Medical School, Southeast University, Nanjing, People's Republic of China
| | - Fengan Ding
- Medical School, Southeast University, Nanjing, People's Republic of China
| | - Qi Gao
- Department of Ultrasonography, Zhong Da Hospital, Medical School, Southeast University, Nanjing, People's Republic of China
| | - Dongsheng Zhang
- Jiangsu Key Laboratory for Biomaterials and Devices, Medical School, Southeast University, Nanjing, People's Republic of China
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Li H, Yan K, Shang Y, Shrestha L, Liao R, Liu F, Li P, Xu H, Xu Z, Chu PK. Folate-bovine serum albumin functionalized polymeric micelles loaded with superparamagnetic iron oxide nanoparticles for tumor targeting and magnetic resonance imaging. Acta Biomater 2015; 15:117-26. [PMID: 25595473 DOI: 10.1016/j.actbio.2015.01.006] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 11/28/2014] [Accepted: 01/07/2015] [Indexed: 01/08/2023]
Abstract
Polymeric micelles functionalized with folate conjugated bovine serum albumin (FA-BSA) and loaded with superparamagnetic iron oxide nanoparticles (SPIONs) are investigated as a specific contrast agent for tumor targeting and magnetic resonance imaging (MRI) in vitro and in vivo. The SPIONs-loaded polymeric micelles are produced by self-assembly of amphiphilic poly(HFMA-co-MOTAC)-g-PEGMA copolymers and oleic acid modified Fe3O4 nanoparticles and functionalized with FA-BSA by electrostatic interaction. The FA-BSA modified magnetic micelles have a hydrodynamic diameter of 196.1 nm, saturation magnetization of 5.5 emu/g, and transverse relaxivity of 167.0 mM(-1) S(-1). In vitro MR imaging, Prussian blue staining, and intracellular iron determination studies demonstrate that the folate-functionalized magnetic micelles have larger cellular uptake against the folate-receptor positive hepatoma cells Bel-7402 than the unmodified magnetic micelles. In vivo MR imaging conducted on nude mice bearing the Bel-7402 xenografts after bolus intravenous administration reveals excellent tumor targeting and MR imaging capabilities, especially at 24h post-injection. These findings suggest the potential of FA-BSA modified magnetic micelles as targeting MRI probe in tumor detection.
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Affiliation(s)
- Huan Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Kai Yan
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Hubei University, Wuhan, Hubei 430062, China
| | - Yalei Shang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Lochan Shrestha
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Rufang Liao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Fang Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
| | - Penghui Li
- Department of Physics & Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China
| | - Haibo Xu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
| | - Zushun Xu
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Hubei University, Wuhan, Hubei 430062, China; Department of Physics & Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
| | - Paul K Chu
- Department of Physics & Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
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Multifunctional Polymeric Nano-Carriers in Targeted Drug Delivery. ADVANCES IN DELIVERY SCIENCE AND TECHNOLOGY 2015. [DOI: 10.1007/978-3-319-11355-5_15] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Scialabba C, Licciardi M, Mauro N, Rocco F, Ceruti M, Giammona G. Inulin-based polymer coated SPIONs as potential drug delivery systems for targeted cancer therapy. Eur J Pharm Biopharm 2014; 88:695-705. [DOI: 10.1016/j.ejpb.2014.09.008] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 09/19/2014] [Accepted: 09/22/2014] [Indexed: 02/01/2023]
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Pilapong C, Sitthichai S, Thongtem S, Thongtem T. Smart magnetic nanoparticle-aptamer probe for targeted imaging and treatment of hepatocellular carcinoma. Int J Pharm 2014; 473:469-74. [PMID: 25089503 DOI: 10.1016/j.ijpharm.2014.07.036] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Revised: 07/09/2014] [Accepted: 07/25/2014] [Indexed: 12/21/2022]
Abstract
We report herein the development of a smart magnetic nanoparticle-aptamer probe, or theranostic nanoprobe, which can be used for targeted imaging and as a drug carrier for hepatocellular carcinoma treatment. The theranostic nanoprobe combines the delivery potential of a non-toxic cellulose derivative polymer, specific capability of cancer-specific molecule (DNA-based EpCAM aptamer) and the imaging capability of magnetic iron oxide nanoparticles. Our proof-of-concept design demonstrates efficient in vitro MR imaging of the cancer cells, and enhanced delivery of an anticancer drug into the cancer cells with comparable treatment efficacy.
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Affiliation(s)
- Chalermchai Pilapong
- Center of Excellence for Molecular Imaging (CEMI), Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
| | - Sudarat Sitthichai
- Department of Physics and Material Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Somchai Thongtem
- Department of Physics and Material Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Titipun Thongtem
- Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand
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Laurent S, Saei AA, Behzadi S, Panahifar A, Mahmoudi M. Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opin Drug Deliv 2014; 11:1449-70. [PMID: 24870351 DOI: 10.1517/17425247.2014.924501] [Citation(s) in RCA: 267] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Bearing in mind that many promising drug candidates have the problem of reaching their target site, the concept of advanced drug delivery can play a significant complementary role in shaping modern medicine. Among other nanoscale drug carriers, superparamagnetic iron oxide nanoparticles (SPIONs) have shown great potential in nanomedicine. The intrinsic properties of SPIONs, such as inherent magnetism, broad safety margin and the availability of methods for fabrication and surface engineering, pave the way for diverse biomedical applications. SPIONs can achieve the highest drug targeting efficiency among carriers, since an external magnetic field locally applied to the target organ enhances the accumulation of magnetic nanoparticles in the drug site of action. Moreover, theranostic multifunctional SPIONs make simultaneous delivery and imaging possible. In spite of these favorable qualities, there are some toxicological concerns, such as oxidative stress, unpredictable cellular responses and induction of signaling pathways, alteration in gene expression profiles and potential disturbance in iron homeostasis, that need to be carefully considered. Besides, the protein corona at the surface of the SPIONs may induce few shortcomings such as reduction of SPIONs targeting efficacy. AREAS COVERED In this review, we will present recent developments of SPIONs as theranostic agents. The article will further address some barriers on drug delivery using SPIONs. EXPERT OPINION One of the major success determinants in targeted in vivo drug delivery using SPIONs is the adequacy of magnetic gradient. This can be partially achieved by using superconducting magnets, local implantation of magnets and application of magnetic stents. Other issues that must be considered include the pharmacokinetics and in vivo fate of SPIONs, their biodegradability, biocompatibility, potential side effects and the crucial impact of protein corona on either drug release profile or mistargeting. Surface modification of SPIONs can open up the possibility of drug delivery to intracellular organelles, drug delivery across the blood-brain barrier, modifying metabolic diseases and a variety of other multimodal and/or theranostic applications.
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Affiliation(s)
- Sophie Laurent
- University of Mons, Avenue Maistriau, NMR and Molecular Imaging Laboratory, Department of General, Organic, and Biomedical Chemistry , 19, B-7000 Mons , Belgium
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Jhaveri AM, Torchilin VP. Multifunctional polymeric micelles for delivery of drugs and siRNA. Front Pharmacol 2014; 5:77. [PMID: 24795633 PMCID: PMC4007015 DOI: 10.3389/fphar.2014.00077] [Citation(s) in RCA: 276] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 03/31/2014] [Indexed: 12/18/2022] Open
Abstract
Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend toward designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to “smart,” multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA). The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.
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Affiliation(s)
- Aditi M Jhaveri
- Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA, USA
| | - Vladimir P Torchilin
- Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University Boston, MA, USA
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Singh D, McMillan JM, Liu XM, Vishwasrao HM, Kabanov AV, Sokolsky-Papkov M, Gendelman HE. Formulation design facilitates magnetic nanoparticle delivery to diseased cells and tissues. Nanomedicine (Lond) 2014; 9:469-85. [PMID: 24646020 DOI: 10.2217/nnm.14.4] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Magnetic nanoparticles (MNPs) accumulate at disease sites with the aid of magnetic fields; biodegradable MNPs can be designed to facilitate drug delivery, influence disease diagnostics, facilitate tissue regeneration and permit protein purification. Because of their limited toxicity, MNPs are widely used in theranostics, simultaneously facilitating diagnostics and therapeutics. To realize therapeutic end points, iron oxide nanoparticle cores (5-30 nm) are encapsulated in a biocompatible polymer shell with drug cargos. Although limited, the toxic potential of MNPs parallels magnetite composition, along with shape, size and surface chemistry. Clearance is hastened by the reticuloendothelial system. To surmount translational barriers, the crystal structure, particle surface and magnetic properties of MNPs need to be optimized. With this in mind, we provide a comprehensive evaluation of advancements in MNP synthesis, functionalization and design, with an eye towards bench-to-bedside translation.
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Affiliation(s)
- Dhirender Singh
- Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA
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Upponi JR, Torchilin VP. Passive vs. Active Targeting: An Update of the EPR Role in Drug Delivery to Tumors. NANO-ONCOLOGICALS 2014. [DOI: 10.1007/978-3-319-08084-0_1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Zhang Q, Zhu J, Song L, Zhang J, Kong D, Zhao Y, Wang Z. Engineering magnetic-molecular sequential targeting nanoparticles for anti-cancer therapy. J Mater Chem B 2013; 1:6402-6410. [DOI: 10.1039/c3tb20715c] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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