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  • Title: Reduction-Responsive Polypeptide Micelles for Intracellular Delivery of Antineoplastic Agent.
    Author: Xu W, Ding J, Chen X.
    Journal: Biomacromolecules; 2017 Oct 09; 18(10):3291-3301. PubMed ID: 28877434.
    Abstract:
    Reduction-responsive methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (i.e., mPEG113-b-PBMLC4 and mPEG113-b-PBMLC9) were facilely synthesized through primary amino-initiated ring-opening polymerization (ROP) of disulfide-containing N-carboxyanhydride monomer. The reduction-responsive block copolymers were then investigated for intracellular delivery of antitumor drug after forming smart micelles in vitro and in vivo. The micelles were denoted as P4M and P9M, respectively. Doxorubicin (DOX) was selected as a model chemotherapeutic agent, which was loaded into micelles via hydrophobic interaction. The drug loading efficiency (DLE) were detected to be 55.4 and 61.7 wt % for P4M and P9M, respectively. The loaded micelles, referred as P4M/DOX and P9M/DOX, exhibited spherical morphologies with hydrodynamic radii of 92.3 ± 2.3 and 80.2 ± 2.8 nm, respectively. Compared to P4M/DOX, P9M/DOX with a smaller size exhibited upregulated cell endocytosis and higher cytotoxicity to human breast cancer MCF-7 cells. Furthermore, the loading micelles, especially P9M/DOX, demonstrated improved antitumor efficacy toward an MCF-7 breast tumor-bearing BALB/c nude mouse model compared with free doxorubicin hydrochloride (DOX·HCl). This was also confirmed by the histopathological and immunohistochemical results. The above results demonstrated that the facially prepared smart polypeptide micelles exhibited a potent prospect in intracellular drug delivery in vitro and in vivo.
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