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Stimuli-Responsive gene delivery Nanocarriers for Cancer Therapy

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Nano-Micro Letters 2023年第3期15卷 299-331页

作者： Qingfei Zhang Gaizhen Kuang Wenzhao Li Jinglin Wang Haozhen Ren Yuanjin Zhao Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolHepatobiliary Institute of Nanjing UniversityNanjing 210008People’s Republic of China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001People’s Republic of China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096People’s Republic of China Chemistry and Biomedicine Innovation Center Nanjing UniversityNanjing 210023People’s Republic of China

gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse ***,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene *** this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid ***,synergistic therapy could be achieved when combined with other therapeutic *** review summarizes recent advances in various stimuliresponsive nanocarriers for gene ***,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are ***,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well *** major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

关键词： Stimuli-responsive Nanocarrier gene therapy gene delivery Cancer

Guanidinoamidized Linear Polyethyleneimine for gene delivery

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Chinese Journal of Polymer Science 2015年第6期33卷 908-919页

作者： Bo Zhang Xin-peng Ma Mei-hua Sui Edward Van Kirk Willia m J.Murdoch Maciej Radosz 林能明申有青 Institute for Individualized Medicine Hangzhou First People’s Hospital Laboratory of Clinical Pharmacy Zhejiang Cancer Hospital Department of Chemical and Petroleum Engineering University of Wyoming Center for Bionanoengineering and the State Key Laboratory for Chemical Engineering Department of Chemical and Biological EngineeringZhejiang University Department of Animal Science University of Wyoming

Guanidine was introduced to low molecular weight linear polyethyleneimine （LPEI） via amide groups, to explore the effect of both guanidine degree and pendant chain length on its transfection behavior. The resulting guanidinoamidized LPEIs （GLPEIs） could dramatically reduce LPEI＇s toxicity, enhance its DNA-packaging capability, cellular uptake and therefore transfection efficiency. These polyplexes were taken up very efficiently via caveolae-mediated endocytosis and their transfection efficiencies in ovarian cancer cells were significantly improved compared to native LPEIlok polyplexes. Among these GLPEIs, LPEI-C3-G100 showed higher DNA affinity even than LPEI25k and the highest transfection efficiency, probably due to the optimization of polymer chain flexibility. Of notice, LPEI-C3-G100 polyplexes could more effectively accumulate into cytoplasm than LPEI25k, although the transfection efficiency of LPEI-C3-G100 polyplexes was not superior to that of LPEI25k polyplexes, which would be probably attributed to the more efficient release of LPEI25k polyplexes than LPEI-C3-G100 polyplexes in the cytoplasm.

关键词： Polyethyleneimine Guanidine gene delivery Cellular uptake.

Cross-linked Polyethylenimine as Potential DNA Vector for gene delivery with High Efficiency and Low Cytotoxicity

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Acta Biochimica et Biophysica Sinica 2006年第11期38卷 780-787页

作者： Wei DONG~(1,2) Guang-Hui JIN~1 Shu-Feng LI~(1,3) Qi-Ming SUN~1 Ding-Yuan MA~1 Zi-Chun HUA~1 1 State Key Laboratory of Pharmaceutical Biotechnology,College of Life Science,Nanjing University,Nanjing 210093,China 2 School of Chemical Engineering Nanjing University of Science and Technology,Nanjing 210094,China 3 College of Basic Medical Science,Southeast University,Nanjing 210009,China State Key Laboratory of Pharmaceutical Biotechnology College of Life Science Nanjing UniversityNanjing 210093 China School of Chemical Engineering Nanjing University of Science and TechnologyNanjing 210094 China College of Basic Medical Science Southeast UniversityNanjing 210009 China

Polyethylenimine (PEI) has been known as an efficient gene carrier with the highest cationiccharge *** transfection efficiency of PEI,along with its cytotoxicity,strongly depends on itsmolecular *** enhance its gene delivery efficiency and minimize cytotoxicity,we have synthesizedsmall cross-linked PEI with biodegradable linkages and evaluated their transfection efficiencies in *** study,branched PEI with a molecular weight of 800 Da was cross-linked by small diacrylate[1,4-butanediol diacrylate or ethyleneglycol dimethacrylate (EGDMA)] for 2-6 *** efficiencies of thecross-linked PEI in in vitro transfection of plasmid DNA containing enhanced green fluorescent protein(EGFP) reporter gene were assessed in melanoma B 16F10 cell line and other cell *** cytometrywas used to quantify the cellular entry efficiency of plasmid and the transgene expression *** of the cross-linked PEI in these cells were evaluated by MTT ***-PEI 800-4h,atypical cross-linked PEI reported here,mediated a more efficient expression of reporter gene than thecommercially available 25-kDa branched PEI control,and resulted in a 9-fold increase in gene deliveryin B16F10 cells and a 16-fold increase in 293T cells,while no cytotoxicity was found at the optimizedcondition for gene ***,the transfection activity of polyplexes was preserved in thepresence of serum proteins.

关键词： polyethylenimine gene delivery cytotoxicity B16F10 293T cell line

Modeling the gene delivery process of the needle array-based tissue nanotransfection

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Nano Research 2022年第4期15卷 3409-3421页

作者： Zhigang Li Yi Xuan Subhadip Ghatak Poornachander RGuda Sashwati Roy Chandan K.Sen Indiana Center for Regenerative Medicine and Engineering Indiana University Health Comprehensive Wound CenterDepartment of SurgeryIndiana University School of MedicineIndianapolisIN 46202USA Birck Nanotechnology Center and Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteIN 47907USA

Hollow needle array-based tissue nanotransfection(TNT)presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric *** this work,the gene delivery process of TNT was simulated and experimentally *** adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin *** distribution of nonuniform electric field across the skin results in various electroporation behavior for each *** underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric *** percentage of electroporated cells within the skin structure,with pore radius over 10 nm,increases from 25%to 82%as the applied voltage increases from 100 to 150 V/***,the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based *** delivery distance increased nonlinearly as the applied voltage and pulse number increased,which mainly depends on the diffusion characteristics and electric conductivity of each *** was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery *** work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings.

关键词： tissue nanotransfection silicon needle array hollow needle array electroporation electrophoresis gene delivery

Size-dependent gene delivery of amine-modified silica nanoparticles

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Nano Research 2016年第2期9卷 291-305页

作者： Meihua Yu Yuting Niu Jun Zhang Hongwei Zhang Yannan Yang Elena Taran Siddharth Jambhrunkar Wenyi Gu Peter Thorn Chengzhong Yu Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane QLD 4072 Australia Australian National Fabrication Facility-QLD Node Brisbane QLD 4072 Australia School of Biomedical Sciences The University of Queensland Brisbane QLD 4072 Australia

Silica-based nanoparticles are promising carriers for gene delivery applications. To gain insights into the effect of particle size on gene transfection efficiency, amine-modified monodisperse St6ber spheres （NH2-SS） with diameters of 125, 230, 330, 440, and 570 nm were synthesized. The in vitro transfection efficiencies of NH2-SS for delivering plasmid DNA encoding green fluorescent protein （GFP）（pcDNA3-EGFP, abbreviated as pcDNA, 6.1 kbp） were studied in HEK293T cells. NH2-SS with a diameter of 330 nm （NH2-SS330） showed the highest GFP transfection level compared to NH2-SS particles with other sizes. The transfection efficiency was found as a compromise between the binding capacity and cellular uptake performance of NH2-SS330 and pcDNA conjugates. NH2-SS330 also demonstrated the highest transfection efficiency for plasmid DNA （pDNA） with a bigger size of 8.9 kbp. To our knowledge, this study is the first to demonstrate the significance of particle size for gene transfection efficiency in silica-based gene delivery systems. Our findings are crucial to the rational design of synthetic vectors for gene therapy.

关键词： silica nanoparticles gene delivery plasmid DNA particle sizes cellular uptake

MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases

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Bioactive Materials 2023年第5期23卷 409-437页

作者： Heng Zhou Yan He Wei Xiong Shuili Jing Xingxiang Duan Zhiyun Huang Gurek SNahal Youjian Peng Mingchang Li Yaoqi Zhu Qingsong Ye Center of Regenerative Medicine&Department of Stomatology Renmin Hospital of Wuhan UniversityWuhan430060China Institute of Regenerative and Translational Medicine Tianyou Hospital of Wuhan University of Science and TechnologyWuhanHubei430064China Department of Oral and Maxillofacial Surgery Massachusetts General HospitalHarvard Medical SchoolBoston02114MAUSA School of Dentistry University of QueenslandHerston4006QLDAustralia Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhan430060China Department of Oral and Maxillofacial Surgery Hospital of Taikang Tongji(Wuhan)430050WuhanChina

Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and *** possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and ***,the therapeutic efficacy of MSCs alone remains unsatisfactory in most *** improve some of their abilities,many studies have employed genetic engineering to transfer key genes into *** viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent ***,to date,different modes of gene transfer have specific drawbacks and *** addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing *** methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC *** this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery ***,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.

关键词： Mesenchymal stem cells gene delivery Neurological diseases Viral vector Nonviral vectors

Design,synthesis and evaluation of spermine-based pH-sensitive amphiphilic gene delivery systems: Multifunctional non-viral gene carriers

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Science China Chemistry 2011年第2期54卷 359-368页

作者： XU RongZuo LU Zheng-Rong Departments of Pharmaceutics and Pharmaceutical Chemistry University of Utah Salt Lake City Utah 84108 USA Department of Biomedical Engineering Case Western Reserve University Cleveland OH 44106 USA

Design and development of efficient non-viral gene delivery systems is critical to overcome various barriers for effective intracellular gene *** new spermine-based protonatable surfactants were designed,synthesized and evaluated as non-viral pH-sensitive gene *** carriers formed stable complexes with plasmid DNA at an N/P ratio as low as *** sizes of the carrier/pDNA nanoparticles (N/P = 12) were in the range of 90–130 nm,smaller than that of Lipofectamine2000/pDNA *** pDNA nanoparticles of the carriers exhibited substantially increased hemolysis when pH decreased from 7.4 to *** DNA nanoparticles had low cytotocixity,similar to that of Lipofectamine-2000/pDNA *** pH-sensitive gene carriers with no helper lipids resulted in much higher intracellular transfection and gene expression in U87 cells than Lipofectamine-2000.[N,N′-Bis(oleoylcysteinyl)(β-alanyl-α-lysyl)]-spermine monoamide (SKACO) resulted in the highest luciferase transfection efficiency,more than 400 times higher than that of Lipofectamine-2000,and GFP expression in 71% of transfected U87 *** was identified as a promising lead carrier for efficient gene *** spermine-based pH-sensitive amphiphilic carriers have a potential to be further developed as efficient non-viral multifunctional gene delivery systems.

关键词： gene delivery plasmid DNA pH sensitive multifunctional

Mesoporous silica nanoparticles for drug and gene delivery

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Acta Pharmaceutica Sinica B 2018年第2期8卷 165-177页

作者： Yixian Zhou Guilan Quan Qiaoli Wu Xiaoxu Zhang Boyi Niua Biyuan Wu Ying Huang Xin Pan Chuanbin Wu School of Pharmaceutical Sciences Sun Yat-Sen University Zengcheng District People's Hospital of Guangzhou Qingdao Huanghai University Guangdong Research Center for Drug delivery Systems

Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly,the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.

关键词： Mesoporous silica nanoparticles Poorly soluble drug Cancer therapy Multidrug resistance gene delivery

Design of Dendrimer Modified Carbon Nanotubes for gene delivery

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Chinese Journal of Cancer Research 2007年第1期19卷 1-6页

作者：潘碧峰崔大祥徐萍陈浩刘凤涛李清黄拓尤晓刚邵君鲍晨晨高峰贺蓉舒孟军马勇杰 Department of Bio-Nano Science and Engineering Key Lab for Thin Film and Micro fabrication of Ministry of Education State Key Lab of Micro-Nano Fabrication Technology Institute of Micro-Nano Science and Technology Shanghai Jiao Tong University

To investigate the efficiency of polyamidoamine dendrimer grafted carbon nanotube （dendrimer-CNT） mediated entrance of anti-survivin oligonucleotide into MCF-7 cells, and its effects on the growth of MCF-7 cells. Methods： Antisense survivin oligonucleotide was anchored onto polyamidoamine dendrimer grafted carbon nanotubes to form dendrimer-CNT-asODN complex and the complex was characterized by Zeta potential, AFM, TEM, and 1% agarose gel electrophoresis analysis. Dendrimer-CNT-asODN complexes were added into the medium and incubated with MCF-7 cells. MTT method was used to detect the effects of asODN and dendrimer-CNT-asODN on the growth of MCF-7 cells. TEM was used to observe the distribution of dendrimer-CNT-asODN complex within MCF-7 cells. Results： Successful synthesis of dendrimer-CNT-asODN complexes was proved by TEM, AFM and agarose gel electrophoresis. TEM showed that the complexes were located in the cytoplasm, endosome, and lysosome within MCF-7 cells. When dendrimer-CNT-asODN （1.0 μmol/L） and asODN （1.0 μmol/L） were used for 120 h incubation, the inhibitory rates of MCF-7 cells were （28.22±3.5）% for dendrimer-CNT-asODN complex group, （9.23±0.56）% for only asODN group, and （3.44±0.25）% for dendrimer-CNT group. Dendrimer-CNT-asODN complex at 3.0 μmol/L inhibited MCF-7 cells by （30.30±10.62）%, and the inhibitory effects were in a time- and concentration-dependent manner. Conclusion： Dendrimer-CNT nanoparticles may serve as a gene delivery vector with high efficiency, which can bring foreign gene into cancer cells, inhibiting cancer cell proliferation and markedly enhancing the cancer therapy effects.

关键词： gene delivery Carbon nanotube Polyamidoamine dendrimer Cancer therapy Survivin gene