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 tu...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.展开更多
基金by the National Natural Science Foundation of China(No.81772278).
文摘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.
