Journal
BIOACTIVE MATERIALS
Volume 6, Issue 11, Pages 3744-3755Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.03.026
Keywords
Cyclodextrin-based star copolymer nanoparticle; miR-122; Doxorubicin Sequential release; Hepatoma chemotherapy
Funding
- National Natural Science Foundation of China [81501575, 81802873]
- National Science and Technology Major Project of China [2018ZX10302205]
- Natural Science Foundation of Tianjin [18JCQNJC81300]
- Key Research Project of Tianjin Health Industry [14KG142]
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In this study, a novel nanoparticle system was developed to co-deliver miR-122 and DOX to hepatoma, showing enhanced therapeutic efficacy through sequential release and synergistic actions of the two components. The co-delivery system demonstrated significantly increased anti-tumor effects in vivo compared to individual treatments, indicating its great potential for hepatoma therapy.
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.
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