Issue 14, 2022

Light-responsive nanodrugs co-self-assembled from a PEG-Pt(iv) prodrug and doxorubicin for reversing multidrug resistance in the chemotherapy process of hypoxic solid tumors

Abstract

Hypoxia-induced multi-drug resistance (MDR) often develops in the chemotherapy process of most anticancer drugs (e.g., doxorubicin, DOX) and results in treatment failure in the clinic. Herein, a PEG-Pt(IV) prodrug was co-self-assembled with DOX into nanodrugs (PEG-Pt(IV)@DOX NPs). They can accumulate in tumor sites due to their longer blood retention half-life. Under light irradiation, the PEG-Pt(IV) prodrug can in situ self-generate oxygen (O2) to reduce the hypoxic zone in tumor tissue effectively and simultaneously release active cis-Pt(II) and DOX. The increasing O2 concentration in the tumor tissue can raise the level of reactive oxygen species (ROS) produced from DOX and significantly enhance the cytotoxicity of DOX to inhibit tumor proliferation by combining with active cis-Pt(II). Finally, the hypoxia-induced MDR of DOX can be alleviated. More importantly, the enhanced cytotoxicity of DOX is limited to the tumor site, which can effectively reduce its side effects on normal tissues. In summary, this would be a promising platform for the combination chemotherapy of hypoxia solid tumors in the clinic.

Graphical abstract: Light-responsive nanodrugs co-self-assembled from a PEG-Pt(iv) prodrug and doxorubicin for reversing multidrug resistance in the chemotherapy process of hypoxic solid tumors

Supplementary files

Article information

Article type
Paper
Submitted
11 May 2022
Accepted
25 May 2022
First published
25 May 2022

Biomater. Sci., 2022,10, 3901-3910

Light-responsive nanodrugs co-self-assembled from a PEG-Pt(IV) prodrug and doxorubicin for reversing multidrug resistance in the chemotherapy process of hypoxic solid tumors

T. Chen, S. Xu, W. Huang and D. Yan, Biomater. Sci., 2022, 10, 3901 DOI: 10.1039/D2BM00739H

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