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A Novel Poly(L-glutamic acid) Dendrimer Based Drug Delivery System with Both pH-Sensitive and Targeting Functions
作者:Hui Yuan, Kui Luo, Yusi Lai, Yuji Pu, Bin He*, Gang Wang, Yao Wu, Zhongwei Gu*
关键字:Poly(L-glutamic acid) dendrimer, targeting, drug delivery, doxorubicin, pH-sensitive
论文来源:期刊
具体来源:Mol. Pharm., 2010, 7: 953-962
发表时间:2010年

The functionalization of pH-sensitiveness and cellular targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity. In this paper, a poly(L-glutamic acid) dendrimer based drug delivery system with both pH-sensitive and targeting functions is reported. Poly(L-glutamic acid) dendrimers with a polyhedral oligomeric silsesquioxane (POSS) nanocubic core were synthesized. Its globular morphology and compact structure with multiple peripheral functional groups made it suitable for drug delivery. The OASG3-Glu dendrimer was conjugated with doxorubicin via pH-sensitive hydrazine bonds and targeting moiety (biotin). The cellular internalization and antitumor effects of the conjugates was evaluated in vitro. Both DLS and TEM results indicated that the conjugates aggregated into nanoparticles with diameters around 50 nm. The release rates of doxorubicin at pH 5.0 were much faster than those at pH 7.0 due to the acid cleavage of the hydrazine bonds. The internalization study revealed that the cellular uptake of the biotin modified conjugates was mainly through receptor-mediated endocytosis. These results indicate that our poly(L-glutamic acid) dendrimers with OAS core are promising vectors for fabricating smart and targeting drug delivery systems.