中文摘要：

采用液相多肽合成方法,成功制备得到窄分子量分布、结构确定的聚乙二醇嵌段共聚四代树枝状聚赖氨酸（MPEG-block-DPL4）.在此基础上,进一步将其DPL4的端氨基转化为端肼基,并通过其与抗肿瘤药物阿霉素（DOX）C=O的反应形成C=N键,实现在DPL4表面的阿霉素药物分子化学结合,最终得到新型pH敏感性的高分子药物MPEG-block-DPL4-CONHN=DOX.运用紫外分光光度（UV-Vis）法,对MPEG-block-DPL4-CONHNH2与阿霉素的负载效率进行了定量分析.高分子药物MPEG-block-DPL4-CONHN=DOX在生理条件（pH=7.4）下相对稳定,而弱酸性条件（pH=4.5,5.5）下,C=N键能较快水解,释放阿霉素药物分子.体外细胞毒性评价结果表明（细胞株SMMC-7721和SPCA-1）,所得新型高分子药物MPEG-block-DPL4-CONHN=DOX的细胞毒性显著地低于游离阿霉素药物分子,因此,可进一步研究发展成为新型pH敏感性可控缓释高分子抗肿瘤药物载体体系.

英文摘要：

Water-soluble methoxy poly（ethylene glycol）-block-dendritic poly（l-lysine） MPEG-block-DPL4 with 4 generation PLL was synthesized with well-defined structure. Further, their PLL dendron surface amino groups were modified by hydrazine, and were succesively conjugated with antitumor doxorubicin via a pH-sensitive N=C hydrazone linkage. UV-Vis spectra were hereby employed for the prepared MPEG-block-DPL4-CONHN=DOX to quantify the efficiencies of transferring dendron surface function groups and newly attaching doxorubicin molecules. Moreover, the new doxorubicin-conjugated polymeric MPEG-block-DPL4-CONHN=DOX was utilized to explore drug release behavior under various pH environments, and indicating that the polymeric drug was quite stable under the physiological condition （pH=7.4） while its DOX drug release was accelerated under acidic condition （pH=4.5, 5.5）. Concerning the cytotoxcity of new synthesized polymeric drug, in-vitro cell toxcity assayed by MTT with human hepatocarcinoma cell-line SMMC-7721 and human lung carcinoma cell-line SPCA-I clearly demonstrated that the new MPEG-block-DPL4-CONHN=DOX showed much lowered cell toxicities than the control of free doxorubicin. Therefore, this low toxcity doxorubicin-conjugated polymeric molecule may be further developed as potential pH-responsive antitumor drug carriar with controlled release ofdoxorubicin.