In vivo tumor targeting of ODN-PEG-folic acid/PEI polyelectrolyte complex micelles
In vivo tumor targeting of ODN-PEG-folic acid/PEI polyelectrolyte complex micelles
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DOI：
10.1163/156856205774472335
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发表时间：
2005-01-01
影响因子：
3.6
通讯作者：
Park, TG
中科院分区：
文献类型：
--
作者：
Jeong, JH;Kim, SH;Park, TG
报道了一种基于聚电解质复合体(PEC)胶束的肿瘤靶向反义寡核苷酸(ODN)递送系统。采用异构化的聚乙二醇交联剂合成了ODN-聚乙二醇叶酸(ODN-PEG-FA)。通过ODN-PEG-FA与聚乙烯亚胺(PEI)之间的离子相互作用，制备了用于肿瘤细胞靶向ODN传递的PEC胶束。用小鼠肿瘤模型评估了PEC胶束的体内靶向特性。ODN-PEG-FA/PEI PEC胶束的粒径为92.3 nm，分布较窄。与ODN-PEG/PEI PEC胶束相比，叶酸受体过表达细胞(KB)对ODN-PEG-FA/PEI PEC胶束的摄取能力显著增强。当ODN-PEG-FA/PEI PEC胶束系统地注射到荷KB细胞移植瘤的小鼠体内时，ODN以靶向的方式聚集到实体瘤中。这项研究表明，表面带有受体可识别靶向配体的PEC胶束具有将ODN药物被动和主动靶向输送到癌细胞的潜力。
A tumor-targeting antisense oligodeoxynucleotide (ODN) delivery system based on polyelectrolyte complex (PEC) micelles is demonstrated. ODN-PEG-folic acid (ODN-PEG-FA) was synthesized using a heterofunctional PEG linker. The PEC micelles for the targeted ODN delivery to tumor cells were produced by ionic interactions between the ODN-PEG-FA and polyethylenimine (PEI). The in vivo targeting properties of the PEC micelles were assessed using a mouse tumor model. The size of ODN-PEG-FA/PEI PEC micelles was 92.3 nm with a relatively narrow distribution. Cellular uptake of the ODN-PEG-FA/PEI PEC micelles by folic acid receptor over-expressing cells (KB) was greatly enhanced compared to that of ODN-PEG/PEI PEC micelles. When the ODN-PEG-FA/PEI PEC micelles were systemically administered to the mice bearing KB cell xenograft tumor, ODN was accumulated to the solid tumor in a target specific manner. This study suggests that the PEC micelles with a receptor-recognizable targeting ligand on the surface have potential for passive and active targeted delivery of ODN drugs to cancer cells.