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Fabrication of doxorubicin-loaded ellipsoid micelle based on diblock copolymer with a linkage of enzyme-cleavable peptide.

Colloids and surfaces. B, Biointerfaces (2015-07-06)
Haitao Huang, Jianqi Geng, Jafar Golzarian, Jin Huang, Jiahui Yu
ABSTRACT

In this study, a novel micellar drug carrier was fabricated from an amphiphilic diblock copolymer containing poly (ethylene glycol) monomethyl ether (mPEG) and stearic moiety (C18) with a linkage of valine-citrulline (VC), which can be cleaved by cathepsin B (CB) enriched in lysosome of tumor cell. Moreover, the self-assembled micelles were observed as ellipsoid shape with major and minor axis of ca. 169 and 103nm, respectively. Such drug carrier was used to encapsulate anti-cancer drug doxorubicin (DOX), and hence showed a faster drug release behavior in a mimic lysosome condition containing cathepsin B. It was ascribed to the lysosome-sensitivity of the valine-citrulline linkage, which was verified by the size distribution curve shifted to greater size under the same mimic lysosome condition. Furthermore, in comparison with pristine doxorubicin, the encapsulation strategy of as-fabricated micellar carrier resulted in a predominant decrease of cytotoxicity. On the whole, a micellar drug carrier, which can be disassembled by cathepsin B, has been emerging as a potential of specific drug release in lysosome. Additionally, the controlled nanoscale together with elongated structure of such assembled ellipsoid micelles might contribute passive targeting function to tumor tissue and faster cellular uptake behavior (Zhou et al.).

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