Zinc-doped Prussian Blue Nanoparticles for Mutp53-carrying Tumor Ion Interference and Photothermal Therapy

Overview

Journal Asian J Pharm Sci

Date 2022 Nov 16

PMID 36382302

Authors

Quanyi Jin

Wenbao Zuo

Qian Lin

Ting Wu

Cong Liu

Nian Liu

Jinxue Liu

Xuan Zhu

Affiliations

Soon will be listed here.

Abstract

Quite a great proportion of known tumor cells carry mutation in TP53 gene, expressing mutant p53 proteins (mutp53) missing not only original genome protective activities but also acquiring gain-of-functions that favor tumor progression and impede treatment of cancers. Zinc ions were reported as agents cytocidal to mutp53-carrying cells by recovering p53 normal functions and abrogating mutp53. Meanwhile in a hyperthermia scenario, the function of wild type p53 is required to ablate tumors upon heat treatment hence the effects might be hindered in a mutp53 background. We herein synthesized zinc-doped Prussian blue (ZP) nanoparticles (NPs) to combine Zn based and photothermal therapeutic effects. An efficient release of Zn in a glutathione-enriched tumor intracellular microenvironment and a prominent photothermal conversion manifested ZP NPs as zinc ion carriers and photothermal agents. Apoptotic death and autophagic mutp53 elimination were found to be induced by ZP NPs in R280K mutp53-containing MDA-MB-231 cells and hyperthermia was rendered to ameliorate the treatment through further mutp53 elimination and increased cell death. The combinatorial therapeutic effect was also confirmed in a mouse model. This study might expand zinc delivery carriers and shed a light on potential interplay of hyperthermia and mutp53 degradation in cancer treatment.

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