自组装槲皮素-Fe^(3+)纳米颗粒用于协同近红外光触发的低温光热/谷胱甘肽激活化学动力学治疗

Self-assembled quercetin-Fe^(3+)nanoparticles for synergetic near-infrared light-triggered low-temperature photothermal/glutathione-activated chemodynamic therapy

光热疗法(PTT)与化学动力疗法(CDT)相结合是一种有效的癌症治疗策略.然而,高温诱导的热休克反应和低Fenton反应效率限制了其临床应用.在这里,我们提出了自组装槲皮素-Fe^(3+)纳米颗粒(Qu-Fe NPs)用于协同近红外(NIR)光触发低温PTT (LTPTT)和谷胱甘肽(GSH)激活CDT.Qu-Fe NPs具有较宽的吸收范围,可延伸至近红外区域,光热转换能力良好.这些NPs在进入癌细胞后,释放出来的Qu可下调HSP70的表达,以实现LTPTT.此外,Qu-Fe NPs可以消耗癌细胞中的GSH,增加癌细胞对活性氧的敏感性.同时,Fe^(3+)可以被还原为Fe^(2+),与内源性H_(2)O_(2)反应生成羟基自由基,实现CDT.PTT产生的热量可以进一步加速CDT中的Fenton反应,从而导致LTPTT与CDT之间的协同效应.实验结果表明,Qu-Fe NPs能有效抑制肿瘤生长.这项工作提出了一种新的方法来实现LTPTT/CDT的联合治疗.

Combining photothermal therapy(PTT)with chemodynamic therapy(CDT)is an efficacious strategy for cancer treatment.However,the hyperthermia-induced heat shock response and low Fenton reaction efficiency limited its clinical application.Here,we present self-assembled quercetin-Fe^(3+)nanoparticles(Qu-Fe NPs)for synergetic near-infrared(NIR)light-triggered low-temperature PTT(LTPTT)and glutathione(GSH)-activated CDT.Qu-Fe NPs had a broad absorption range extending to the NIR region and excellent photothermal conversion ability.After endocytosis into cancer cells,these NPs partially released Qu that downregulated the expression of heat shock protein 70,in turn allowing for LTPTT.Moreover,Qu-Fe NPs could deplete the overexpressed GSH in cancer cells,increasing their sensitivity to reactive oxygen species.Meanwhile,Fe^(3+)could be reduced to Fe^(2+),which can react with endogenous H_(2)O_(2) to generate hydroxyl radicals to achieve CDT.Heat generated by PTT could further accelerate the Fenton reaction in CDT,thus resulting in the synergistic effects between LTPTT and CDT.Both in vitro and in vivo results showed that Qu-Fe NPs could effectively inhibit tumor growth.This work presents a new approach for achieving mutually reinforced,synergetic NPs that can be used for LTPTT/CDT combination therapy.