Yoo Hyuk Sang, Lee Eun Ah, Park Tae Gwan
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305-701, South Korea.
J Control Release. 2002 Jul 18;82(1):17-27. doi: 10.1016/s0168-3659(02)00088-3.
Doxorubicin was chemically conjugated to the terminal end of a di-block copolymer composed of poly(L-lactic acid) (PLLA) and methoxy-poly(ethylene glycol) (mPEG) via two acid-cleavable linkages. A hydrazone bond and a cis-acotinyl bond were formed between doxorubicin and the terminal group of PLLA segment in the block copolymer. Doxorubicin-conjugated PLLA-mPEG di-block copolymers self-assembled to form micelles in aqueous solution. The doxorubicin-conjugated micelles were about 89.1 nm in diameter and their critical micelle concentration was 1.3 microg/ml. These values were comparable with those of unconjugated micelles. In an acidic condition, the conjugated doxorubicin in the hydrazone linkage was readily cleaved, releasing doxorubicin in an intact structure. Doxorubicin-conjugated PLLA-mPEG micelles were more potent in cell cytotoxicity than free doxorubicin, suggesting that they were more easily taken up within cells with concomitant rapid release of cleaved doxorubicin into the cytoplasm from acidic endosomes.
阿霉素通过两个酸可裂解键化学偶联到由聚（L-乳酸）（PLLA）和甲氧基聚（乙二醇）（mPEG）组成的双嵌段共聚物的末端。在阿霉素与嵌段共聚物中PLLA链段的末端基团之间形成了腙键和顺式阿可丁基键。阿霉素偶联的PLLA-mPEG双嵌段共聚物在水溶液中自组装形成胶束。阿霉素偶联的胶束直径约为89.1nm，其临界胶束浓度为1.3μg/ml。这些值与未偶联的胶束相当。在酸性条件下，腙键连接的偶联阿霉素很容易裂解，以完整结构释放阿霉素。阿霉素偶联的PLLA-mPEG胶束在细胞毒性方面比游离阿霉素更强，这表明它们更容易被细胞摄取，同时裂解的阿霉素从酸性内体快速释放到细胞质中。
