Reduction-sensitive platinum (IV)-prodrug nano-sensitizer with an ultra-high drug loading for efficient chemo-radiotherapy of Pt-resistant cervical cancer in vivo.

Journal of Controlled Release : Official Journal of the Controlled Release Society
Kejun LuoZhihua Gan

Abstract

Cisplatin is widely used in the chemoradiotherapy (CRT) of cervical cancers. However, despite the severe systemic side effects, the therapeutic efficacy of cisplatin is often compromised by the development of drug resistance, which is closely related to the elevated intracellular thiol-containing species (especially glutathione (GSH)) and the adenosine triphosphate (ATP)-dependent glutathione S-conjugate pumps. The construction of a safe and redox-sensitive nano-sensitizer with high disulfide density and high Pt(IV) prodrug loading capacity (up to 16.50% Pt and even higher), as described herein, is a promising way to overcome the cisplatin resistance and enhance the CRT efficacy. The optimized nanoparticles (NPs) (referred to as SSCV5) with moderate Pt loading (7.62% Pt) and median size (c.a. 40 nm) was screened out and used for further biological evaluation. Compared with free cisplatin, more drugs could be transported and released inside the cisplatin resistant cells (Hela-CDDP) by SSCV5 NPs. With the synergistic effect of GSH scavenging and mitochondrial damage, SSCV5 NPs can easily reverse the cisplatin resistance. Moreover, the higher nucleus DNA binding Pt content of SSCV5 NPs not only caused the DNA damage and apoptosis ...Continue Reading

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Citations

Apr 20, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhiyuan Zhong
Jun 8, 2021·Frontiers in Bioengineering and Biotechnology·Shengnan YangZhirong Bao
Oct 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Raut BholakantJan Feijen
Oct 26, 2021·Advanced Materials·Kuikun YangXiaoyuan Chen

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