阳离子型纳米载体在递送抗肿瘤药物过程中的细胞转运机制及影响因素的研究概况
摘要
目的:综述阳离子型纳米载体在递送抗肿瘤药物过程中的细胞转运机制及影响因素,为阳离子型纳米载体介导的肿瘤靶向给药系统的设计提供参考。方法:以"阳离子载体""细胞摄取""胞内转运""细胞外排""Cationic carrier""Cell uptake""Intracellular transportation""Exocytosis"等为关键词,组合查询2000年1月-2018年9月收录在中国知网、万方数据、维普网、PubMed、Elsevier等数据库中的相关文献,对阳离子型纳米载体在递送抗肿瘤药物过程中的细胞转运机制及影响因素进行归纳总结。结果与结论:共检索到相关文献488篇,其中有效文献44篇。阳离子型纳米载体在递送抗肿瘤药物过程中的细胞转运过程包括细胞摄取、胞内转运、细胞外排3个过程。细胞摄取机制包括能量依赖的内吞作用和细胞膜打孔,其影响因素有阳离子型纳米载体及其给药系统的粒径、肿瘤细胞的种类;胞内转运机制即阳离子型纳米载体被摄取后部分转运至溶酶体,部分避开溶酶体转运至细胞浆或其他细胞器,其是否转运进入溶酶体主要由内吞途径决定;细胞外排机制即阳离子型纳米载体通过外泌体、溶酶体降解和内质网-高尔基体-细胞膜途径被排出肿瘤细胞,其影响因素有肿瘤细胞种类和阳离子型纳米载体的粒径、形状及其在细胞内的分布。细胞内部分细胞器具有带电荷的膜结构,阳离子型纳米载体可能会与细胞器膜发生静电作用,从而影响其靶向作用,但该作用机制仍需要进一步深入研究,以期为开发靶向性更强、抗肿瘤效果更好的肿瘤靶向给药系统提供参考。
引文
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[29]LUZIO JP,PARKINSON MD,GRAY SR,et al.The delivery of endocytosed cargo to lysosomes[J].Biochem Soc Trans,2009,37(Pt5):1019-1021.
[30]BENGALI Z,REA JC,SHEA LD.Gene expression and internalization following vector adsorption to immobilized proteins:dependence on protein identity and density[J].J Gene Med,2007,9(8):668-678.
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[34]CHAI GH,HU FQ,SUN J,et al.Transport pathways of solid lipid nanoparticles across madin darby canine kidney epithelial cell monolayer[J].Mol Pharm,2014,11(10):3716-3726.
[35]BASTOS N,RUIVO CF,DA SILVA S,et al.Exosomes in cancer:use them or target them?[J].Semin Cell Dev Biol,2018.DOI:10.1016/j.semcdb.2017.08.009.
[36]SAFAEI R,LARSON BJ,CHENG TC,et al.Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells[J].Mol Cancer Ther,2005,4(10):1595-1604.
[37]MILANE L,SINGH A,MATTHEOLABAKIS G,et al.Exosome mediated communication within the tumor microenvironment[J].J Control Release,2015.DOI:10.1016/j.jconrel.2015.06.029.
[38]UN K,SAKAI-KATO K,OSHIMA Y,et al.Intracellular trafficking mechanism,from intracellular uptake to extracellular efflux,for phospholipid/cholesterol liposomes[J].Biomaterials,2012.DOI:10.1016/j.biomaterials.2012.07.030.
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[40]PANYAM J,LABHASETWAR V.Dynamics of endocytosis and exocytosis of poly(D,L-lactide-co-glycolide)nanoparticles in vascular smooth muscle cells[J].Pharm Res,2003,20(2):212-220.
[41]CHITHRANI BD,CHAN WC.Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes[J].Nano Lett,2007,7(6):1542-1550.
[42]CHU Z,HUANG Y,TAO Q,et al.Cellular uptake,evolution,and excretion of silica nanoparticles in human cells[J].Nanoscale,2011,3(8):3291-3299.
[43]STAYTON I,WINIARZ J,SHANNON K,et al.Study of uptake and loss of silica nanoparticles in living human lung epithelial cells at single cell level[J].Anal Bioanal Chem,2009,394(6):1595-1608.
[44]WANG Z,LI N,ZHAO J,et al.CuO nanoparticle interaction with human epithelial cells:cellular uptake,location,export,and genotoxicity[J].Chem Res Toxicol,2012,25(7):1512-1521.
[2]YOSHIZAKI Y,YUBA E,SAKAGUCHI N,et al.pH-sensitive polymer-modified liposome-based immunity-inducing system:effects of inclusion of cationic lipid and CpG-DNA[J].Biomaterials,2017.DOI:10.1016/j.biomaterials.2017.07.001.
[3]MARQUEZ-MIRANDA V,PENALOZA JP,ARAYA-DURAN I,et al.Effect of terminal groups of dendrimers in the complexation with antisense oligonucleotides and cell uptake[J].Nanoscale Res Lett,2016,11(66):1-13.
[4]XIANG S,TONG H,SHI Q,et al.Uptake mechanisms of non-viral gene delivery[J].J Control Release,2012,158(3):371-378.
[5]FROHLICH E.The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles[J].Int JNanomedicine,2012.DOI:10.2147/IJN.S36111.
[6]SUN NF,LIU ZA,HUANG WB,et al.The research of nanoparticles as gene vector for tumor gene therapy[J].Crit Rev Onco Hematol,2014.DOI:10.1016/j.critrevonc.2013.10.006.
[7]CUI SH,ZHI DF,ZHAO YN,et al.Cationic lioposomes with folic acid as targeting ligand for gene delivery[J].Bioorg Med Chem Lett,2016,26(16):4025-4029.
[8]WANG MY,HU HY,SUN YQ,et al.A pH-sensitive gene delivery system based on folic acid-PEG-chitosanPAMAM-plasmid DNA complexes for cancer cell targeting[J].Biomaterials,2013.DOI:10.1016/j.biomaterials.2013.09.006.
[9]PATRI AK,MAJOROS IJ,BAKER JR.Dendritic polymer macromolecular carriers for drug delivery[J].Curr Opin Chem Bio,2002.DOI:10.1016/S1367-5931(02)00347-2.
[10]THOMMEY PT,MAJOROS I,KOTHIYAR A,et al.Cationic poly(amidoamine)dendrimer induces lysosomal apoptotic pathway at therapeutically relevant concentrations[J].Biomacromolecules,2009,10(12):3207-3214.
[11]PERUMAL OP,INAPAGOLLA R,KANNAN S,et al.The effect of surface functionality on cellular trafficking of dendrimers[J].Biomaterials,2008.DOI:10.1016/j.biomaterials.2008.04.038.
[12]SAKHTIANCHI R,MINCHIN RF,LEE KB,et al.Exocytosis of nanoparticles from cells:role in cellular retention and toxicity[J].Adv Colloid Interface Sci,2013.DOI:10.1016/j.cis.2013.10.013.
[13]IVERSEN TG,SKOTLAND T,SANDVIG K.Endocytosis and intracellular transport of nanoparticles:present knowledge and need for future studies[J].Nano Today,2011.DOI:10.1016/j.nantod.2011.02.003.
[14]SAHAY G,ALAKHOVA DY,KABANOV AV.Endocytosis of nanomedicines[J].J Control Release,2010,145(3):182-195.
[15]YANES RE,TARN D,HWANG AA,et al.Involvement of lysosomal exocytosis in the excretion of mesoporous silica nanoparticles and enhancement of the drug delivery effect by exocytosis inhibition[J].Small,2013,9(5):697-704.
[16]HONG S,LEROUEILl PR,JANUS EK,et al.Interaction of polycationic polymers with supported lipid bilayers and cells:nanoscale hole formation and enhanced membrane permeability[J].Bioconjug Chem,2006,17(3):728-734.
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[18]VERCAUTEREN D,REJMAN J,MARTENS TF,et al.On the cellular processing of non-viral nanomedicines for nucleic acid delivery:mechanisms and methods[J].J Control Release,2012,161(2):566-581.
[19]黄海华.药学细胞生物学[M].北京:中国医药科技出版社,2006:125-129.
[20]王洪刚,高萌,张成鸿,等.青藤碱PLGA-TPGS纳米粒的制备及人肝癌HepG2细胞对其摄取、被其抑制的作用研究[J].中国药房,2016,27(13):1811-1814.
[21]NICHOLS B.Caveosomes and endocytosis of lipid rafts[J].J Cell Sci,2003,116(Pt23):4707-4714.
[22]LIU C,YU W,CHEN Z,et al.Enhanced gene transfection efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic acid)-poly(ethylene glycol)nanoparticles through caveolae-mediated endocytosis[J].JControl Release,2011,151(2):162-175.
[23]ZHANG J,LIU D,ZHANG MJ,et al.The cellular uptake mechanism,intracellular transportation,and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells[J].Int J Nanomedicine,2016.DOI:10.2147/IJN.S106418.
[24]LEROUEIL PR,BERRY SA,DUTHIE K,et al.Wide varieties of cationic nanoparticles induce defects in supported lipid bilayers[J].Nano Lett,2008,8(2):420-424.
[25]HONG S,BIELINSKA AU,MECKE A,et al.Interaction of poly(amidoamine)dendrimers with supported lipid bilayers and cells:hole formation and the relation to transport[J].Bioconjug Chem,2004,15(4):774-782.
[26]REJMAN J,OBERLE V,ZUHORN IS,et al.Size-dependent internalization of particles via the pathways of clathrin-and caveolae mediated endocytosis[J].Biochem J,2004,377(Pt1):159-169.
[27]REJMAN J,BRAGONZI A,CONESE M.Role of clathrin-and caveolae-mediated endocytosis in gene transfer mediated by lipo-and polyplexes[J].Mol Ther,2005,12(3):468-474.
[28]SEIB FP,JONES AT,DUNCAN R.Comparison of the endocytic properties of linear and branched PEIs,and cationic PAMAM dendrimers in B16f10 melanoma cells[J].JControl Release,2007,117(3):291-300.
[29]LUZIO JP,PARKINSON MD,GRAY SR,et al.The delivery of endocytosed cargo to lysosomes[J].Biochem Soc Trans,2009,37(Pt5):1019-1021.
[30]BENGALI Z,REA JC,SHEA LD.Gene expression and internalization following vector adsorption to immobilized proteins:dependence on protein identity and density[J].J Gene Med,2007,9(8):668-678.
[31]ZHANG XJ,CHEN DW,BA S,et al.Poly(l-histidine)based triblock copolymers:pH induced reassembly of copolymer micelles and mechanism underlying endolysosomal escape for intracellular delivery[J].Biomacromolecules,2014,15(11):4032-4045.
[32]REINHOLZ J,DIESLER C,SCHOTTLER S,et al.Protein machineries defining pathways of nanocarrier exocytosis and transcytosis[J].Acta Biomater,2018.DOI:10.1016/j.actbio.2018.03.006.
[33]DING L,ZHU X,WANG Y,et al.Intracellular fate of nanoparticles with polydopamine surface engineering and a novel strategy for exocytosis-inhibiting,lysosome impairment-based cancer therapy[J].Nano Lett,2017,17(11):6790-6801.
[34]CHAI GH,HU FQ,SUN J,et al.Transport pathways of solid lipid nanoparticles across madin darby canine kidney epithelial cell monolayer[J].Mol Pharm,2014,11(10):3716-3726.
[35]BASTOS N,RUIVO CF,DA SILVA S,et al.Exosomes in cancer:use them or target them?[J].Semin Cell Dev Biol,2018.DOI:10.1016/j.semcdb.2017.08.009.
[36]SAFAEI R,LARSON BJ,CHENG TC,et al.Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells[J].Mol Cancer Ther,2005,4(10):1595-1604.
[37]MILANE L,SINGH A,MATTHEOLABAKIS G,et al.Exosome mediated communication within the tumor microenvironment[J].J Control Release,2015.DOI:10.1016/j.jconrel.2015.06.029.
[38]UN K,SAKAI-KATO K,OSHIMA Y,et al.Intracellular trafficking mechanism,from intracellular uptake to extracellular efflux,for phospholipid/cholesterol liposomes[J].Biomaterials,2012.DOI:10.1016/j.biomaterials.2012.07.030.
[39]LING H,ZHENG M,ZHANG Y,et al.Influences of size of silica particles on the cellular endocytosis,exocytosis and cell activity of HepG2 cells[J].J Nanosci Lett,2011,1(1):1-16.
[40]PANYAM J,LABHASETWAR V.Dynamics of endocytosis and exocytosis of poly(D,L-lactide-co-glycolide)nanoparticles in vascular smooth muscle cells[J].Pharm Res,2003,20(2):212-220.
[41]CHITHRANI BD,CHAN WC.Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes[J].Nano Lett,2007,7(6):1542-1550.
[42]CHU Z,HUANG Y,TAO Q,et al.Cellular uptake,evolution,and excretion of silica nanoparticles in human cells[J].Nanoscale,2011,3(8):3291-3299.
[43]STAYTON I,WINIARZ J,SHANNON K,et al.Study of uptake and loss of silica nanoparticles in living human lung epithelial cells at single cell level[J].Anal Bioanal Chem,2009,394(6):1595-1608.
[44]WANG Z,LI N,ZHAO J,et al.CuO nanoparticle interaction with human epithelial cells:cellular uptake,location,export,and genotoxicity[J].Chem Res Toxicol,2012,25(7):1512-1521.