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Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition.

ABSTRACT: Chemotherapy, as one of the most commonly used treatment modalities for cancer therapy, provides limited benefits to hepatoma patients, owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma. Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA - miR-122 for enhancing chemo-therapeutic efficacy in hepatoma. Herein, a cyclodextrin-cored star copolymer nanoparticle system (sCDP/DOX/miR-122) is constructed to co-deliver miR-122 with doxorubicin (DOX) for hepatoma therapy. In this nanosystem, miR-122 is condensed by the outer cationic poly (2-(dimethylamino) ethyl methacrylate) chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities, endowing a sequential release manner of miR-122 and DOX. The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity, but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression, which realizes synergistic performance on cell inhibition. Moreover, sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone, indicating its great promising in hepatoma therapy.

SUBMITTER: Xiong Q

PROVIDER: S-EPMC8056416 | biostudies-literature |

REPOSITORIES: biostudies-literature

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