高等学校化学学报2012，Vol.33Issue(12)：2809-2815,7.DOI:10.7503/cjcu20120137
肿瘤酸度响应性聚(L-赖氨酸)-阿霉素键合药的制备与表征
Synthesis and Characterization of Tumor-acidity-sensitive Poly (L-lysine)-doxorubicin Conjugates
摘要
Abstract
Succinic anhydride ( SA) and cw-aconitic anhydride ( CA) were used to modify doxorubicin (DOX), obtaining acid-insensitive SA-DOX (SAD) and acid-sensitive CA-DOX(CAD), respectively. SAD or CAD, and carboxyl group terminated monomethoxyl poly(ethylene glycol) (mPEG-COOH) were conjugated onto poly (L-lysine) (PLL), yielding acid-insensitive PLL-g-mPEG/SAD and acid-sensitive PLL-g-mPEG/ CAD, respectively. The chemical structures of PLL-DOX conjugates were characterized by H NMR and FTIR. The drug conjugating content was determined with UV-Vis spectrophotometer. Dynamic laser scattering (DLS) measurements revealed that the amphiphilic PLL-DOX conjugates could self-assemble into nanoparti-cles in phosphate buffer(PB) at pH = 7. 4. In vitro release profiles revealed that the DOX release from PLL-g-mPEG/CAD could be accelerated at acid conditions(pH = 5. 3 and 6. 8) , while that from PLL-g-mPEG/SAD was slow at all test pH(5. 3, 6. 8 and 7. 4). The acid-sensitive DOX release from PLL-g-mPEG/CAD conjugates ensured higher concentration of free DOX in tumor and more pronounced antitumor efficacy. In vitro methyl thiazolyl tetrazolium assay demonstrated that PLL-g-mPEG/CAD had enhanced tumor proliferation inhibition activity comparing with acid-insensitive PLL-g-mPEG/SAD. Therefore, PLL-g-mPEG/CAD conjugates might be further developed as potential smart antitumor drugs with controlled DOX release.关键词
阿霉素/聚(L-赖氨酸)/肿瘤酸度响应性/肿瘤细胞增殖抑制Key words
Doxorubicin/ Poly (L-lysine) / Tumor-acidity-sensitive/ Tumor cell proliferation inhibition分类
化学化工引用本文复制引用
张建成,丁建勋,肖春生,贺超良,庄秀丽,杨亚楠,陈学思..肿瘤酸度响应性聚(L-赖氨酸)-阿霉素键合药的制备与表征[J].高等学校化学学报,2012,33(12):2809-2815,7.基金项目
国家自然科学基金(批准号:51103015,50733003,20904053,51003103,21174142和50973108)资助. （批准号:51103015,50733003,20904053,51003103,21174142和50973108）
