L-Cystine-Crosslinked Polypeptide Nanogel as aReduction-Responsive Excipient for Prostate Cancer Chemotherapy

Smart polymer nanogel-assisted drug delivery systems have attracted more and more attention in cancer chemotherapy because of their well-defined morphologies and pleiotropic functions in recent years. In this work, an L-cystine-crosslinked reduction-responsive polypeptide nanogel of methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine) (mPEG-P(LP-co-LC)) was employed as a smart excipient for RM-1 prostate cancer (PCa) chemotherapy. Doxorubicin (DOX), as a regular chemotherapy drug, was embedded in the nanogel. The loading nano gel marked as NG/DOX was shown to exhibit glutathione (GSH)-induced swelling and GSH-accelerated DOX release. Subsequently, NG/DOX showed efficient cellular uptake and proliferation inhibition. Furthermore, NG/DOX presented enhanced antitumor efficacy and security in an RM-1 PCa-grafted mouse model in vivo, indicating its great potential for clinical treatment.

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L-Cystine-Crosslinked Polypeptide Nanogel as aReduction-Responsive Excipient for Prostate Cancer Chemotherapy
Liang He 1,2,†, Di Li 2,†, Zhongtang Wang 3,*, Weiguo Xu 2, Jixue Wang 1,2, Hui Guo 1,2,
Chunxi Wang 1,* and Jianxun Ding 2,*
1 Department of Urology, the First Hospital of Jilin University, Changchun 130021, China;
lianghe9278@126.com (L.H.); wangjx@ciac.ac.cn (J.W.); 18443154199@163.com (H.G.)
2 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy
of Sciences, Changchun 130022, China; lidi@ciac.ac.cn (D.L.); wgxu@ciac.ac.cn (W.X.)
3 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan 250117, China
* Correspondence: zhongtangw@163.com (Z.W.); chunxi_wang@126.com (C.W.); jxding@ciac.ac.cn (J.D.);
Tel.: +86-531-6762-6162 (Z.W.); +86-431-8878-2321 (C.W.); +86-431-8526-2116 (J.D.)
† These authors contributed equally to this work.
Academic Editor: Carsten Werner
Received: 19 December 2015; Accepted: 26 January 2016; Published: 29 January 2016
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