基于糖原的可成像基因载体
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摘要
现有的基因载体由于较高的细胞毒性和单一的功能性在生物医药领域的应用受到限制,糖原是一种动物淀粉,是由葡萄糖结合而成的支链多糖,具有良好的生物相容性和生物可降解性,以糖原为骨架,利用糖原上的羟基引入原子转移自由基聚会(ATRP)引发点,制备得到以聚甲基丙烯酸N,N-二甲氨基乙酯为侧链的阳离子基因载体Gly-co-PDs,该载体侧链上的氨基可进行后续修饰,进一步被金粒子功能化后得到Gly-co-PD-Au载体,并对该载体的基因络合能力、基因释放能力、细胞毒性和CT成像能力进行研究,研究表明:该载体与目前商业化的基因载体聚乙烯亚胺和聚甲基丙烯酸二甲氨基乙酯相比,具有更优异的基因运载能力,更低的细胞毒性和独特的CT成像功能,因此该载体可用于癌细胞基因治疗的实时可成像CT造影,在实现实时成像的基因治疗方面有潜在应用价值。
Nowday, the gene vectors are limited in the field of biomedicine due to their high cytotoxicity and single functionality. Glycogen is an animal starch with branched chain composed of glucose and has good biocompatibility and biodegradability. In this work, a series of cationic gene vectors comprising glycogen backbones and poly(2-(dimethylamino) ethyl methacrylate)(PDMAEMA) side chains with different lengths(termed as Gly-co-PDs) were readily prepared by atom transfer radical polymerization(ATRP). Gly-co-PDs could be further modified with gold nanoparticles which can be termed as Gly-co-PD-Au. The gene condensation ability, buffering ability and cytotoxicity of Gly-co-PDs and Gly-co-PD-Au carriers were investigated. Gly-co-PD-Au exhibits excellent gene delivery capacity, low cytotoxicity and CT imaging function. Such Gly-co-PD-Au vectors which could be utilized as a CT contrast agent for cancer cell imaging has potential application in real-time imaging for gene therapy.
Nowday, the gene vectors are limited in the field of biomedicine due to their high cytotoxicity and single functionality. Glycogen is an animal starch with branched chain composed of glucose and has good biocompatibility and biodegradability. In this work, a series of cationic gene vectors comprising glycogen backbones and poly(2-(dimethylamino) ethyl methacrylate)(PDMAEMA) side chains with different lengths(termed as Gly-co-PDs) were readily prepared by atom transfer radical polymerization(ATRP). Gly-co-PDs could be further modified with gold nanoparticles which can be termed as Gly-co-PD-Au. The gene condensation ability, buffering ability and cytotoxicity of Gly-co-PDs and Gly-co-PD-Au carriers were investigated. Gly-co-PD-Au exhibits excellent gene delivery capacity, low cytotoxicity and CT imaging function. Such Gly-co-PD-Au vectors which could be utilized as a CT contrast agent for cancer cell imaging has potential application in real-time imaging for gene therapy.
引文
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[2]DONG R,SU Y,YU S,et al.A redox-responsive cationic supramolecular polymer constructed from small molecules as a promising gene vector[J].Chem.Commun.,2013,49:9845-9847.
[3]张敏,邬军文,姚昀,等.聚乙烯亚胺及其配位聚合物凝胶在基因载体中的应用[J].药学服务与研究,2017,17(6):411-414.
[4]LIU J,XU Y,YANG Q,et al.Reduction biodegradable brushed PDMAEMA derivatives synthesized by atom transfer radical polymerization and click chemistry for gene delivery[J].Acta Biomater.,2013,9:7758-7766.
[5]LI J,CHENG D,YIN T,et al.Copolymer of poly(ethylene glycol)and poly(L-lysine)grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery[J].Nanoscale,2014,6:1732-1740.
[6]LIANG X,REN X Y,LIU Z Z,et al.An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives[J].Int.J.Nanomed.,2014,9:419-435.
[7]YANG X C,NIU Y L,ZHAO N N,et al.A biocleavable pullulan-based vector via ATRP for liver cell-targeting gene delivery[J].Biomaterials,2014,35:3873-3884.
[8]胡浩.基于PDMAEMA修饰的不同形貌纳米颗粒构建高性能基因载体[D].北京:北京化工大学,2016.
[9]LIU H,XU Y,WEN S,et al.Facile hydrothermal synthesis of low generation dendrimer-stabilized gold nanoparticles for in vivo computed tomography imaging applications[J].Polym.Chem.,2013,4:1788.
[10]LIU Y,AI K,LIU J,et al.A high-performance Ytterbium-based nanoparticulate contrast agent for in vivo X-ray computed tomography imaging[J].Angew.Chem.Int.Edit.,2012,51:1437-1442.
[11]赵文静.基于金纳米复合材料的仿生合成及其在CT/MRI中的应用[D].上海:上海师范大学,2018.
[12]YAN P,ZHAO N,HU H,et al.A facile strategy to functionalize gold nanorods with polycation brushes for biomedical applications[J].Acta Biomater.,2014,10:3786-3794.