Zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy

作     者：Quanyi Jin Wenbao Zuo Qian Lin Ting Wu Cong Liu Nian Liu Jinxue Liu Xuan Zhu Quanyi Jin;Wenbao Zuo;Qian Lin;Ting Wu;Cong Liu;Nian Liu;Jinxue Liu;Xuan Zhu

作者机构：Fujian Provincial Key Laboratory of Innovative Drug Target ResearchSchool of Pharmaceutical SciencesXiamen UniversityXiamen 361005China Cancer Research CenterSchool of MedicineXiamen UniversityXiamen 361000China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2022年第17卷第5期

页      面：767-777页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：by the National Natural Science Foundation of China(No.81772278). 

主　　题：Zinc Mutant p53 Prussian blue Photothermal therapy Ion interference therapy 

摘      要：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 2+based and photothermal therapeutic effects.An efficient release of Zn 2+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 in vitro through further mutp53 elimination and increased cell death.The combinatorial therapeutic effect was also confirmed in vivo 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.