Irinotecan delivery by unimolecular micelles composed of reduction-responsive star-like polymeric prodrug with high drug loading for enhanced cancer therapy
2018
Gao, Yong-E. | Bai, Shuang | Shi, Xiaoxiao | Hou, Meili | Ma, Xiaoqian | Zhang, Tian | Xiao, Bo | Xue, Peng | Kang, Yuejun | Xu, Zhigang
Nanomedicine based polymeric prodrug have showed high impact in the inhibition of tumor growth due to its high therapeutic efficiency and improved biocompatibility. Herein, we synthesized a novel star-like amphiphilic copolymer [β-CD–P(Ir-co-OEGMA), denoted as CPIO] through atom transfer radical polymerization (ATRP) to deliver the hydrophilic anticancer drug irinotecan (Ir). The polymer could form monodisperse unimolecular micelles and had excellent stability in aqueous solution. Moreover, the reduction-responsive feature of the micelles facilitated controlled release of drug, thus achieving targeted therapy and reduced toxicity to healthy cells. The in vitro cytotoxicity assays indicated that CPIO had a notable anticancer effect against HeLa and MCF-7 tumor cells. The confocal laser scanning microscopy and flow cytometry experiments revealed that CPIO micelles could be internalized into tumor cells efficiently. Furthermore, the obtained prodrug micelles produced better efficacy compared to free Ir. Moreover, the CPIO micelles showed excellent biocompatibility in vivo after intravenous injection on a mouse model. This study demonstrated that CPIO carrier could provide a rational design of a stimuli-responsive polymeric prodrug for delivery of irinotecan.
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