期刊
BIOMATERIALS
卷 277, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121071
关键词
Cascade nanoreactor; Metal-organic frameworks; Oxidative stress; Chemotherapy; Nanomedicine
资金
- National Key R&D Program of China [2016YFA0203700]
- National Natural Science Foundation of China [51722211, 51672303, 32171391, 51902336]
- Program of Shanghai Subject Chief Scientist [18XD1404300]
- Development Fund for Shanghai Talents [2018114]
This study successfully established a tumor-specific nanoreactor to activate cascade reactions inside tumor cells, enhancing the therapeutic effects of chemotherapy and oxidative stress and leading to augmented antitumor efficacy.
Catalytic cascade transformations, which occur in spatially constrained tumor environment to generate therapeutic moieties from prodrugs or intrinsic species, are highly desirable for precise cancer therapy. Nevertheless, it is high challenging to engineer a cascade nanoreactor with tumor microenvironment (TME)-responsive capability for synergistic tumor therapy. Inspired by the biocatalytic cascades in biological processes, here, a tumor-specific nanoreactor was established to activate cascade reactions for oxidative stress-augmented chemotherapy by the integration of an artificial enzyme, Pt(IV)-based prodrug (Pt(IV)), with Cu(II)-based metal-organic frameworks (CuMOF). Upon internalization of CuMOF@Pt(IV) by tumor cells, in addition to chemotherapeutic effect, the activated cisplatin by glutathione (GSH) reduction is capable of acting as an artificial enzyme to elevate the hydrogen peroxide (H2O2) level through cascade reactions for augmenting the therapeutic efficacy of Cu+-mediated chemodynamic therapy (CDT). Meanwhile, CuMOF@Pt(IV) specifically deplete overexpressed GSH at tumor sites, thus amplifying tumor oxidative stress, and finally leading to augmented antitumor efficacy. The orchestrated cooperative effect of chemotherapy and oxidative stress presents splendid therapeutic efficacy on tumor-bearing mice with negligible adverse effects. Therefore, this cascade nanoreactor provides exciting opportunities to develop complementary therapeutic modalities for precise cancer treatment.
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