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由甲氧基聚乙二醇-g-α,β-聚[(N-氨基酸基)-DL-天冬酰胺]和顺二氯二氨铂(II)制备聚合物-铂(II)配合物纳米胶束及其细胞毒性

Fabrication of polymer-platinum(II) complex nanomicelle from mPEG-g-alpha,beta-poly [(N-amino acidyl)-DL-aspartamide] and cis-dichlorodiammine platinum(II) and its cytotoxicity.

作者信息

Wang Chengyun, Gong Yanbao, Fan Naiqian, Liu Shunying, Luo Shufang, Yu Jiahui, Huang Jin

机构信息

College of New Drug Innovation Research & Development, East China Normal University, Shanghai 200062, PR China.

出版信息

Colloids Surf B Biointerfaces. 2009 Apr 1;70(1):84-90. doi: 10.1016/j.colsurfb.2008.12.012. Epub 2008 Dec 11.


DOI:10.1016/j.colsurfb.2008.12.012
PMID:19150231
Abstract

The aim of research is to develop and optimize delivery system for cis-dichlorodiammine platinum(II) (CDDP) based on polymer-metal complex nanomicelles with controllable particle size in order to achieve the passive tumor targeting. In particular, graft copolymers, mPEG-g-alpha,beta-poly [(N-amino acidyl)-DL-aspartamide] (mPEG-g-PAAsp) were synthesized by the ring-opening reaction of polysuccinimide with mPEG-NH(2) (M(w): 2000 and 5000 Da), and then with l-aspartic acid and l-glutamic acid, respectively. mPEG-g-PAAsp-CDDP complex nanomicelles were fabricated from mPEG-g-PAAsp and CDDP. The formation of mPEG-g-PAAsp-CDDP nanomicelles was confirmed by fluorescence spectrophotoscopy, electrical conductivity and particle size measurements. It was found that all the nanomicelles showed spherical shapes with clear core-shell structures and narrow size distributions. Their sizes ranged from 80 to 160 nm, suggesting of their passive targeting potential to tumor tissue. With the increase of the molecular weight of mPEG, the sizes of mPEG-g-PAAsp-CDDP micelles showed a tendency to increase. mPEG-g-PAAsp-CDDP nanomicelles showed linear gradual drug release profiles in 40 h, suggestion of their sustained drug release behaviors. Compared with CDDP, mPEG-g-PAAsp-CDDP micelles showed essential decreased cytotoxicity to Bel-7402 cell line.

摘要

本研究旨在开发并优化基于聚合物-金属络合物纳米胶束的顺二氯二氨铂(II)(CDDP)递送系统,该纳米胶束粒径可控,以实现被动肿瘤靶向。具体而言,通过聚琥珀酰亚胺与mPEG-NH(2)(分子量:2000和5000 Da)的开环反应,然后分别与L-天冬氨酸和L-谷氨酸反应,合成了接枝共聚物mPEG-g-α,β-聚[(N-氨基酸基)-DL-天冬酰胺](mPEG-g-PAAsp)。由mPEG-g-PAAsp和CDDP制备了mPEG-g-PAAsp-CDDP复合纳米胶束。通过荧光分光光度法、电导率和粒径测量证实了mPEG-g-PAAsp-CDDP纳米胶束的形成。结果发现,所有纳米胶束均呈球形,具有清晰的核壳结构且粒径分布狭窄。其粒径范围为80至160 nm,表明它们具有被动靶向肿瘤组织的潜力。随着mPEG分子量的增加,mPEG-g-PAAsp-CDDP胶束的粒径呈增大趋势。mPEG-g-PAAsp-CDDP纳米胶束在40小时内呈现线性逐渐释药曲线,表明其具有持续释药行为。与CDDP相比,mPEG-g-PAAsp-CDDP胶束对Bel-7402细胞系的细胞毒性显著降低。

相似文献

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[2]
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引用本文的文献

[1]
Nanocarriers for delivery of platinum anticancer drugs.

Adv Drug Deliv Rev. 2013-10-8

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