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 OAS-G(3)-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.

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Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC) 2 , is the crucial DSF's metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu(II) and carboxylic groups in poly(ethylene glycol)-b-poly(ester-carbonate) (PEC) for efficient loading of Cu(DDC) 2 , which was generated by the in situ reaction of DSF and Cu(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu(II), and PEC. These Cu(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu(DDC) 2 -based chemotherapy and chemodynamic therapy mediated by bioavailable Cu(II) that was not in the form of Cu(DDC) 2 . The in vivo antitumor results demonstrated that the Cu(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.

Platinum-based chemotherapy is widely used to treat various cancers. However, exogenous platinum is apt to cause severe side effects and drug resistance induced by upregulated glutathione (GSH) in cancer cells...

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