Bioreducible PAA-g-PEG graft micelles with high doxorubicin loading for targeted antitumor effect against mouse breast carcinoma

Nanomaterials have demonstrated to be promising to deliver a chemotherapeutic drug deeply into the tumor for improving the anticancer efficacy. In this study, eight kinds of bioreducible PAA-g-PEG graft copolymeric micelles were prepared, and the anticancer drug DOX was stably encapsulated in the micelles. Benefited by the hydrophobic interaction and pi-pi stacking between aromatic structure of DOX and phenyl of PAA in the micelle core, high drug loading content more than 50 wt/wt % could be achieved. Drugs released from micelles in a reduction-sensitive manner, and effectively inhibit the growth of 411 mouse breast cancer cells in vitro. In the 4T1 tumor-bearing nude mice breast carcinoma subcutaneous model, the DOX-incorporated micelles showed much stronger accumulation in tumor than DOX center dot HCI, and reduced distribution in other main organs. The antitumor effect of the micelles was significantly better than DOX center dot HCI, as confirmed by tumor volume and body weight changes of the tumor-bearing Balb/c mice, as well as survive study. Encapsulation of DOX in the micelles improved the bioavailability of the drugs through the accumulation in tumor by passive targeting, greatly decreased organ damage due to cancer cell wild growth and metastasis, and depressed the toxicity of DOX on the heart and other organs. (C) 2013 Elsevier Ltd. All rights reserved.