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  • Title: Starburst Diblock Polyprodrugs: Reduction-Responsive Unimolecular Micelles with High Drug Loading and Robust Micellar Stability for Programmed Delivery of Anticancer Drugs.
    Author: Shi X, Hou M, Ma X, Bai S, Zhang T, Xue P, Zhang X, Liu G, Kang Y, Xu Z.
    Journal: Biomacromolecules; 2019 Mar 11; 20(3):1190-1202. PubMed ID: 30658038.
    Abstract:
    Polymeric prodrug based on therapeutic nanomedicine has demonstrated great promise for effective tumor growth inhibition, however, the drawbacks of low drug-loading and weak micellar stability limit its application for clinical cancer therapy. Herein, a reduction-responsive starburst block copolymer prodrug CCP [β-cyclodextrin (β-CD)-PCPTXX-POEGMA, XX: SS or CC] has been developed for cancer therapy. And CCP is composed of β-CD-Br core with multiple reactive sites, as well as a diblock copolymer containing hydrophobic polymerized camptothecin (PCPT) prodrug chain and hydrophilic poly[(ethylene glycol) methyl ether methacrylate] (OEGMA) chain. A family of CCP polymeric prodrugs with different drug loading contents (up to 25%) and various sizes of unimolecular micelles (UMs) (around 30 nm) were obtained by adjusting the block ratio of PCPTXX and POEGMA. On account of the amphiphilic structure feature, CPP could take shape water-soluble UMs in aqueous medium with excellent micellar stability. Under imitatively reductive tumor microenvironment, anticancer drug CPT could rapidly escape from CCP UMs in terms of disulfide bond breakage. However, this behavior is strongly refrained in the physiological environment. In vitro and in vivo outcome confirmed that CCP UMs showed excellent performance of sufficient tumor accumulation, high-efficiency tumor growth inhibition and low-toxicity for healthy tissues. Based on these gratifying therapeutic efficacy, it is believed that as-present starburst prodrug strategy can offer a brand-new insight for high-efficiency therapeutic nanoplatforms for chemotherapy application.
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