化学
两亲性
乙二醇
谷胱甘肽
氧化应激
生物物理学
体内
激进的
过氧化氢
活性氧
喜树碱
组合化学
生物化学
聚合物
有机化学
酶
生物技术
生物
共聚物
作者
Jie Xu,Jiajia Tan,Chengzhou Song,Guoying Zhang,Xianglong Hu,Shiyong Liu
标识
DOI:10.1002/ange.202303829
摘要
Abstract Amphiphilic self‐immolative polymers (SIPs) can achieve complete degradation solely through one triggerable event, which potentially optimize the blood clearance and uncontrollable/inert degradability for therapeutic nanoparticles. Herein, we report self‐immolative amphiphilic poly(ferrocenes), BP nbs ‐Fc , composed by self‐immolative backbone and aminoferrocene (AFc) side chains as well as end‐capping poly(ethylene glycol) monomethyl ether. Upon triggering by tumor acidic milieu, the BP nbs ‐Fc nanoparticles readily degrade to release azaquinone methide (AQM) moieties, which can rapidly deplete intracellular glutathione (GSH) to cascade release AFc. Furthermore, both AFc and its product Fe 2+ can catalyze intracellular hydrogen peroxide (H 2 O 2 ) into highly reactive hydroxyl radicals (⋅OH), thus amplifying the oxidative stress of tumor cells. Rational synergy of GSH depletion and ⋅OH burst can efficiently inhibit tumor growth by the SIPs in vitro and in vivo. This work provides an elegant design to adopt innate tumor milieu‐triggerable SIPs degradation to boost cellular oxidative stress, which is a promising candidate for precision medicine.
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