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-1 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 of doxorubicin.

Key words: poly(ethylene glycol)-block-dendritic poly(l-lysine), doxorubicin, pH-responsive, controlled drug release