基于脂质体的纳米基因载体的研究进展
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摘要
基因治疗是指将外源基因导入目标细胞,用以修正因基因缺陷和异常导致的疾病,达到治疗疾病的目的。外源基因在细胞中高效、持续地表达是基因治疗成功的关键,这与载体的选择息息相关。随着科技的发展,脂质体纳米复合物作为基因载体受到人们广泛关注,其具有功能多样、易于修饰、生物相容性好、转染效率高等优点。本文介绍了脂质体的结构特点,并对磁性纳米、金纳米、量子点、壳聚糖、上转换纳米与脂质体的复合物作为基因载体进行综述和展望。
Gene therapy is a method for curing diseases caused by genetic defects and anomalies through introducing normal foreign genes into targeted cells. Efficient and sustained expression of foreign genes in cells is the decisive factor in gene therapy,which is significantly relied on the vectors used in the treatment. With the development of science and technology,the research of liposome/nanocomposites as gene carriers has widely attracted people' s attention, due to the following advantages: versatile functions, easy surface modification,good biocompatibility,high transfection efficiency. Herein,the structure of liposome bilayer was introduced and the complexes of magnetic nanoparticles, gold nanoparticles, quantum dots, chitosan,upconversion nanoparticles with liposomes as gene carriers have been reviewed and prospected.
Gene therapy is a method for curing diseases caused by genetic defects and anomalies through introducing normal foreign genes into targeted cells. Efficient and sustained expression of foreign genes in cells is the decisive factor in gene therapy,which is significantly relied on the vectors used in the treatment. With the development of science and technology,the research of liposome/nanocomposites as gene carriers has widely attracted people' s attention, due to the following advantages: versatile functions, easy surface modification,good biocompatibility,high transfection efficiency. Herein,the structure of liposome bilayer was introduced and the complexes of magnetic nanoparticles, gold nanoparticles, quantum dots, chitosan,upconversion nanoparticles with liposomes as gene carriers have been reviewed and prospected.
引文
[1]Loh X J,Ong S J,Tung Y T,et al.Co-delivery of Drug and DNA from Cationic Dual-responsive Micelles Derived from Poly(DMAEMA-co-PPGMA)[J].Mater Sci Eng:C,2013,33(8):4545-4550.
[2]El-Aneed A.An Overview of Current Delivery Systems in Cancer Gene Therapy[J].J Control Release,2004,94(1):1-14.
[3]Koo H,Huh M S,Sun I C,et al.In vivo Targeted Delivery of Nanoparticles for Theranosis[J].Acc Chem Res,2011,44(10):1018-1028.
[4]ZHANG Yangde.Nanopharmacy[M].Beijing:Chemical Industry Press,2015:60-61(in Chinese).张阳德.纳米药物学[M].北京:化学工业出版社,2015:60-61.
[5]SUN Bo.Preparation of Ivermectin Liposomes and Their Effects on Drug Distribution in Sheep[D].Beijing:China Agricultural University,2003(in Chinese).孙博.伊维菌素脂质体的制备及其对药物在绵羊体内分布的影响[D].北京:中国农业大学,2003.
[6]CHEN Jixiang,LI Guanglin.New Advances in the Application of Liposomes in Biology[J].Gansu Anim Husband Veterin Med,2000,30(3):28-29(in Chinese).陈吉祥,李广林.脂质体在生物学中的应用新进展[J].甘肃畜牧兽医,2000,30(3):28-29.
[7]LI Xiuying,ZENG Fan,ZHAO Yao,et al.Research Progress of Liposome Drug Delivery System[J].Chinese J New Drugs,2014,23(16):1904-1911(in Chinese).李秀英,曾凡,赵曜,等.脂质体药物递送系统的研究进展[J].中国新药杂志,2014,23(16):1904-1911.
[8]Zhang S,Gibson L,Preece D,et al.Viscoelasticity Measurements Inside Liposomes[C]//Optical Trapping and Optical Micromanipulation XI.International Society for Optics and Photonics,2014,9164:91642O.
[9]van der Westen R,Hosta-Rigau L,Sutherland D S,et al.Myoblast Cell Interaction with Polydopamine Coated Liposomes[J].Biointerphases,2012,7(1/2/3/4):8-16.
[10]Huang Z,Liu Y H,Zhang Y M,et al.Cyclen-based Cationic Lipids Containing a p H-sensitive Moiety as Gene Delivery Vectors[J].Org Biomol Chem,2015,13(2):620-630.
[11]Bangham A D,Standish M M,Watkins J C,et al.Diffusion of Univalentions Across the Lamellae of Swollen Phospholipids[J].J Mol Biol,1965,13(1):238-252.
[12]Sessa G,Weissmann G.Phospholipid Spherules(liposomes)as a Model for Biological Membranes[J].J Lipid Res,1968,9(3):310-318.
[13]HU Jianjun,QIAO Weihong,LI Zongshi.Application of Liposomes in Drug Controlled Release and Gene Therapy[C].Seventh International Conference on Surfactant Detergent Proceedings.Taiyuan:Shanxi Chemical Industry Press,2002(in Chinese).胡剑均,乔卫红,李宗石.脂质体在药物控释与基因治疗中的应用[C].七届国际表面活性剂洗涤剂会议论文集.太原:山西化工出版社,2002.
[14]DANG Qifeng,LIU Chengsheng,YAN Jingquan,et al.Preparation and Physicochemical Properties of Carboxymethyl Chitosan Coated VELiposomes[J].J Funct Mater,2011,42(9):1631-1634(in Chinese).党奇峰,刘成圣,颜景泉,等.羧甲基壳聚糖包覆VE脂质体的制备及理化性质研究[J].功能材料,2011,42(9):1631-1634.
[15]ZHANG Chengxiang,ZHAO Weiyu,LWanliang.Preparation of Multifunctional Targeting Epirubicin Liposomes and Their Inhibitory Effect on Glioma Cells[J].Chinese Pharm J,2015,5(14):1208-1214(in Chinese).张诚翔,赵炜煜,吕万良.多功能靶向性表柔比星脂质体的制备及其对脑胶质瘤细胞的抑制效应[J].中国药学杂志,2015,5(14):1208-1214.
[16]YANG Tong.Advances in Novel Liposomes[J].Herald Med,2009,28(3):336-338(in Chinese).杨彤.新型脂质体的研究进展[J].医药导报,2009,28(3):336-338.
[17]Yu Q,Hu X,Ma Y,et al.Lipids-based Nanostructured Lipid Carriers(NLCs)for Improved Oral Bioavailability of Sirolimus[J].Drug Deliv,2016,23(4):1469-1475.
[18]Balguri S P,Adelli G R,Majumdar S.Topical Ophthalmic Lipid Nanoparticle Formulations(SLN,NLC)of Indomethacin for Delivery to the Posterior Segment Ocular Tissues[J].Eur J Pharm Biopharm,2016,109:224-235.
[19]Esposito E,Ravani L,Drechsler M,et al.Cannabinoid Antagonist in Nanostructured Lipid Carriers(NLCs):Design,Characterization and in vivo Study[J].Mater Sci Eng:C,2015,48:328-336.
[20]WANG Qin,GONG Yuefa,YANG Xiangliang.Recent Advances of Gene Carrier Cationic Polymers[J].J Guangdong Pharm Univ,2004,20(1):62-64(in Chinese).王勤,龚跃法,杨祥良.基因载体阳离子聚合物的研究进展[J].广东药学院学报,2004,20(1):62-64.
[21]Namiki Y,Namiki T,Yoshida H,et al.A Novel Magnetic Crystal-Lipid Nanostructure for Magnetically Guided in vivo Gene Delivery[J].Nat Nanotechnol,2009,4(9):598-606.
[22]Holzbach T,Vlaskou D,Neshkova I,et al.Non-viral VEGF(165)Gene Therapy-Magnetofection of Acoustically Active Magnetic Lipospheres(Magnetobubbles')Increases Tissue Survival in an Oversized Skin Flapmodel[J].J Cell Mol Med,2008,14(3):587-599.
[23]Pan X,Guan J,Yoo J W,et al.Cationic Lipid-coated Magnetic Nanoparticles Associated with Transferrin for Gene Delivery[J].Int J Pharm,2008,358(1):263-270.
[24]Heun Y,Hildebrand S,Heidsieck A,et al.Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo[J].Theranostics,2017,7(2):295-307.
[25]Gao D,Lin X P,Zhang Z P,et al.Intracellular Cargo Delivery by virus Capsid Protein-based Vehicles:From Nano to Micro[J].Nanomed-Nanotechnol,2016,12(2):365-376.
[26]Zhao Z,Zhou Z,Bao J,et al.Octapod Iron Oxide Nanoparticles as High-Performance T2Contrast Agents for Magnetic Resonance Imaging[J].Nat Commun,2013,4:2266-2272.
[27]Oliver M,Ahmad A,Kamaly N,et al.MAGfect:A Novel Liposome Formulation for MRI Labelling and Visualization of Cells[J].Org Biomol Chem,2006,4(18):3489-3497.
[28]Luo X,Li B,Zhang X,et al.Dual-functional Lipid-like Nanoparticles for Delivery of mRNA and MRI Contrast Agents[J].Nanoscale,2017,9(4):1575-1579.
[29]Li P C,Li D,Zhang L,et al.Cationic Lipid Bilayer Coated Gold Nanoparticles-Mediated Transfection of Mammalian Cells[J].Biomaterials,2008,29(26):3617-3624.
[30]Li D,Li P C,Li G,et al.The Effect of Nocodazole on the Transfection Efficiency of Lipid-Bilayer Coated Gold Nanoparticles[J].Biomaterials,2009,30(7):1382-1388.
[31]Du B,Gu X,Han X,et al.Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo[J].Chem Med Chem,2017,12(21):1768-1775.
[32]WU Feng,CAI Jiye.Application of Quantum Dots in Cancer Research[J].Acta Laser Biol Sin,2007,16(6):800-804(in Chinese).吴峰,蔡继业.量子点在癌症研究中的应用[J].激光生物学报,2007,16(6):800-804.
[33]Shao D,Li J,Pan Y,et al.Noninvasive Theranostic Imaging of HSV-TK/GCV Suicide Gene Therapy in Liver Cancer by Folate-Targeted Quantum Dot-based Liposomes[J].Biomater Sci,2015,3(6):833-841.
[34]Kim M W,Jeong H Y,Kang S J,et al.Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles[J].Sci Rep,2017,7(1):9474-9484.
[35]Murata J,Ohya Y,Ouchi T.Possibility of Application of Quaternary Chitosan Having Pendant Galactose Residues as Gene Delivery Tool[J].Carbohydr Polym,1996,29(1):69-74.
[36]Baghdan E,Pinnapireddy S R,Strehlow B,et al.Lipid Coated Chitosan-DNA Nanoparticles for Enhanced Gene Delivery[J].Int J Pharm,2018,535(1):473-479.
[37]Tezgel,Szarpak-Jankowska A,Arnould A,et al.Chitosan-Lipid Nanoparticles(CS-LNPs):Application to siRNA Delivery[J].J Colloid Interface Sci,2018,510:45-56.
[38]Wang L,Yan R,Huo Z,et al.Fluorescence Resonant Energy Transfer Biosensor Based on Upconversion-Luminescent Nanoparticles[J].Angew Chem Int Ed,2005,44(37):6054-6057.
[39]Chen Z,Chen H,Hu H,et al.Versatile Synthesis Strategy for Carboxylic Acid-Functionalized Upconverting Nanophosphors as Biological Labels[J].J Am Chem Soc,2008,130(10):3023-3029.
[40]Song C,Zhang S,Zhou Q,et al.Bifunctional Cationic Solid Lipid Nanoparticles ofβ-Na YF4∶Yb,Er Upconversion Nanoparticles Coated with a Lipid for Bioimaging and Gene Delivery[J].RSC Adv,2017,7(43):26633-26639.
[41]Duan G,Kang S,Tian X,et al.Protein Corona Mitigates the Cytotoxicity of Graphene Oxide by Reducing Its Physical Interaction with Cell Membrane[J].Nanoscale,2015,7(37):15214-15224.
[42]Chong Y,Ge C,Yang Z,et al.Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating[J].ACS Nano,2015,9(6):5713-5724.
[43]Imani R,Shao W,Taherkhani S,et al.Dual-functionalized Graphene Oxide for Enhanced siRNA Delivery to Breast Cancer Cells[J].Colloid Surf B,2016,147:315-325.
[44]Zhang L,Yao H J,Yu Y,et al.Mitochondrial Targeting Liposomes Incorporating Daunorubicin and Quinacrine for Treatment of Relapsed Breast Cancer Arising from Cancer Stem Cells[J].Biomaterials,2012,33(2):565-582.
[45]Ma X,Zhou J,Zhang C X,et al.Modulation of Drug-Resistant Membrane and Apoptosis Proteins of Breast Cancer Stem Cells by Targeting Berberine Liposomes[J].Biomaterials,2013,34(18):4452-4465.
[2]El-Aneed A.An Overview of Current Delivery Systems in Cancer Gene Therapy[J].J Control Release,2004,94(1):1-14.
[3]Koo H,Huh M S,Sun I C,et al.In vivo Targeted Delivery of Nanoparticles for Theranosis[J].Acc Chem Res,2011,44(10):1018-1028.
[4]ZHANG Yangde.Nanopharmacy[M].Beijing:Chemical Industry Press,2015:60-61(in Chinese).张阳德.纳米药物学[M].北京:化学工业出版社,2015:60-61.
[5]SUN Bo.Preparation of Ivermectin Liposomes and Their Effects on Drug Distribution in Sheep[D].Beijing:China Agricultural University,2003(in Chinese).孙博.伊维菌素脂质体的制备及其对药物在绵羊体内分布的影响[D].北京:中国农业大学,2003.
[6]CHEN Jixiang,LI Guanglin.New Advances in the Application of Liposomes in Biology[J].Gansu Anim Husband Veterin Med,2000,30(3):28-29(in Chinese).陈吉祥,李广林.脂质体在生物学中的应用新进展[J].甘肃畜牧兽医,2000,30(3):28-29.
[7]LI Xiuying,ZENG Fan,ZHAO Yao,et al.Research Progress of Liposome Drug Delivery System[J].Chinese J New Drugs,2014,23(16):1904-1911(in Chinese).李秀英,曾凡,赵曜,等.脂质体药物递送系统的研究进展[J].中国新药杂志,2014,23(16):1904-1911.
[8]Zhang S,Gibson L,Preece D,et al.Viscoelasticity Measurements Inside Liposomes[C]//Optical Trapping and Optical Micromanipulation XI.International Society for Optics and Photonics,2014,9164:91642O.
[9]van der Westen R,Hosta-Rigau L,Sutherland D S,et al.Myoblast Cell Interaction with Polydopamine Coated Liposomes[J].Biointerphases,2012,7(1/2/3/4):8-16.
[10]Huang Z,Liu Y H,Zhang Y M,et al.Cyclen-based Cationic Lipids Containing a p H-sensitive Moiety as Gene Delivery Vectors[J].Org Biomol Chem,2015,13(2):620-630.
[11]Bangham A D,Standish M M,Watkins J C,et al.Diffusion of Univalentions Across the Lamellae of Swollen Phospholipids[J].J Mol Biol,1965,13(1):238-252.
[12]Sessa G,Weissmann G.Phospholipid Spherules(liposomes)as a Model for Biological Membranes[J].J Lipid Res,1968,9(3):310-318.
[13]HU Jianjun,QIAO Weihong,LI Zongshi.Application of Liposomes in Drug Controlled Release and Gene Therapy[C].Seventh International Conference on Surfactant Detergent Proceedings.Taiyuan:Shanxi Chemical Industry Press,2002(in Chinese).胡剑均,乔卫红,李宗石.脂质体在药物控释与基因治疗中的应用[C].七届国际表面活性剂洗涤剂会议论文集.太原:山西化工出版社,2002.
[14]DANG Qifeng,LIU Chengsheng,YAN Jingquan,et al.Preparation and Physicochemical Properties of Carboxymethyl Chitosan Coated VELiposomes[J].J Funct Mater,2011,42(9):1631-1634(in Chinese).党奇峰,刘成圣,颜景泉,等.羧甲基壳聚糖包覆VE脂质体的制备及理化性质研究[J].功能材料,2011,42(9):1631-1634.
[15]ZHANG Chengxiang,ZHAO Weiyu,LWanliang.Preparation of Multifunctional Targeting Epirubicin Liposomes and Their Inhibitory Effect on Glioma Cells[J].Chinese Pharm J,2015,5(14):1208-1214(in Chinese).张诚翔,赵炜煜,吕万良.多功能靶向性表柔比星脂质体的制备及其对脑胶质瘤细胞的抑制效应[J].中国药学杂志,2015,5(14):1208-1214.
[16]YANG Tong.Advances in Novel Liposomes[J].Herald Med,2009,28(3):336-338(in Chinese).杨彤.新型脂质体的研究进展[J].医药导报,2009,28(3):336-338.
[17]Yu Q,Hu X,Ma Y,et al.Lipids-based Nanostructured Lipid Carriers(NLCs)for Improved Oral Bioavailability of Sirolimus[J].Drug Deliv,2016,23(4):1469-1475.
[18]Balguri S P,Adelli G R,Majumdar S.Topical Ophthalmic Lipid Nanoparticle Formulations(SLN,NLC)of Indomethacin for Delivery to the Posterior Segment Ocular Tissues[J].Eur J Pharm Biopharm,2016,109:224-235.
[19]Esposito E,Ravani L,Drechsler M,et al.Cannabinoid Antagonist in Nanostructured Lipid Carriers(NLCs):Design,Characterization and in vivo Study[J].Mater Sci Eng:C,2015,48:328-336.
[20]WANG Qin,GONG Yuefa,YANG Xiangliang.Recent Advances of Gene Carrier Cationic Polymers[J].J Guangdong Pharm Univ,2004,20(1):62-64(in Chinese).王勤,龚跃法,杨祥良.基因载体阳离子聚合物的研究进展[J].广东药学院学报,2004,20(1):62-64.
[21]Namiki Y,Namiki T,Yoshida H,et al.A Novel Magnetic Crystal-Lipid Nanostructure for Magnetically Guided in vivo Gene Delivery[J].Nat Nanotechnol,2009,4(9):598-606.
[22]Holzbach T,Vlaskou D,Neshkova I,et al.Non-viral VEGF(165)Gene Therapy-Magnetofection of Acoustically Active Magnetic Lipospheres(Magnetobubbles')Increases Tissue Survival in an Oversized Skin Flapmodel[J].J Cell Mol Med,2008,14(3):587-599.
[23]Pan X,Guan J,Yoo J W,et al.Cationic Lipid-coated Magnetic Nanoparticles Associated with Transferrin for Gene Delivery[J].Int J Pharm,2008,358(1):263-270.
[24]Heun Y,Hildebrand S,Heidsieck A,et al.Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo[J].Theranostics,2017,7(2):295-307.
[25]Gao D,Lin X P,Zhang Z P,et al.Intracellular Cargo Delivery by virus Capsid Protein-based Vehicles:From Nano to Micro[J].Nanomed-Nanotechnol,2016,12(2):365-376.
[26]Zhao Z,Zhou Z,Bao J,et al.Octapod Iron Oxide Nanoparticles as High-Performance T2Contrast Agents for Magnetic Resonance Imaging[J].Nat Commun,2013,4:2266-2272.
[27]Oliver M,Ahmad A,Kamaly N,et al.MAGfect:A Novel Liposome Formulation for MRI Labelling and Visualization of Cells[J].Org Biomol Chem,2006,4(18):3489-3497.
[28]Luo X,Li B,Zhang X,et al.Dual-functional Lipid-like Nanoparticles for Delivery of mRNA and MRI Contrast Agents[J].Nanoscale,2017,9(4):1575-1579.
[29]Li P C,Li D,Zhang L,et al.Cationic Lipid Bilayer Coated Gold Nanoparticles-Mediated Transfection of Mammalian Cells[J].Biomaterials,2008,29(26):3617-3624.
[30]Li D,Li P C,Li G,et al.The Effect of Nocodazole on the Transfection Efficiency of Lipid-Bilayer Coated Gold Nanoparticles[J].Biomaterials,2009,30(7):1382-1388.
[31]Du B,Gu X,Han X,et al.Lipid-Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo[J].Chem Med Chem,2017,12(21):1768-1775.
[32]WU Feng,CAI Jiye.Application of Quantum Dots in Cancer Research[J].Acta Laser Biol Sin,2007,16(6):800-804(in Chinese).吴峰,蔡继业.量子点在癌症研究中的应用[J].激光生物学报,2007,16(6):800-804.
[33]Shao D,Li J,Pan Y,et al.Noninvasive Theranostic Imaging of HSV-TK/GCV Suicide Gene Therapy in Liver Cancer by Folate-Targeted Quantum Dot-based Liposomes[J].Biomater Sci,2015,3(6):833-841.
[34]Kim M W,Jeong H Y,Kang S J,et al.Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles[J].Sci Rep,2017,7(1):9474-9484.
[35]Murata J,Ohya Y,Ouchi T.Possibility of Application of Quaternary Chitosan Having Pendant Galactose Residues as Gene Delivery Tool[J].Carbohydr Polym,1996,29(1):69-74.
[36]Baghdan E,Pinnapireddy S R,Strehlow B,et al.Lipid Coated Chitosan-DNA Nanoparticles for Enhanced Gene Delivery[J].Int J Pharm,2018,535(1):473-479.
[37]Tezgel,Szarpak-Jankowska A,Arnould A,et al.Chitosan-Lipid Nanoparticles(CS-LNPs):Application to siRNA Delivery[J].J Colloid Interface Sci,2018,510:45-56.
[38]Wang L,Yan R,Huo Z,et al.Fluorescence Resonant Energy Transfer Biosensor Based on Upconversion-Luminescent Nanoparticles[J].Angew Chem Int Ed,2005,44(37):6054-6057.
[39]Chen Z,Chen H,Hu H,et al.Versatile Synthesis Strategy for Carboxylic Acid-Functionalized Upconverting Nanophosphors as Biological Labels[J].J Am Chem Soc,2008,130(10):3023-3029.
[40]Song C,Zhang S,Zhou Q,et al.Bifunctional Cationic Solid Lipid Nanoparticles ofβ-Na YF4∶Yb,Er Upconversion Nanoparticles Coated with a Lipid for Bioimaging and Gene Delivery[J].RSC Adv,2017,7(43):26633-26639.
[41]Duan G,Kang S,Tian X,et al.Protein Corona Mitigates the Cytotoxicity of Graphene Oxide by Reducing Its Physical Interaction with Cell Membrane[J].Nanoscale,2015,7(37):15214-15224.
[42]Chong Y,Ge C,Yang Z,et al.Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating[J].ACS Nano,2015,9(6):5713-5724.
[43]Imani R,Shao W,Taherkhani S,et al.Dual-functionalized Graphene Oxide for Enhanced siRNA Delivery to Breast Cancer Cells[J].Colloid Surf B,2016,147:315-325.
[44]Zhang L,Yao H J,Yu Y,et al.Mitochondrial Targeting Liposomes Incorporating Daunorubicin and Quinacrine for Treatment of Relapsed Breast Cancer Arising from Cancer Stem Cells[J].Biomaterials,2012,33(2):565-582.
[45]Ma X,Zhou J,Zhang C X,et al.Modulation of Drug-Resistant Membrane and Apoptosis Proteins of Breast Cancer Stem Cells by Targeting Berberine Liposomes[J].Biomaterials,2013,34(18):4452-4465.