Affiliation:
1. Department of Pharmacy The First Affiliated Hospital of USTC Division of Life Sciences and Medicine, and Key Laboratory of Precision and Intelligent Chemistry University of Science and Technology of China 96 Jinzhai Road 230026 Hefei Anhui Province China
2. School of Biomedical Engineering Division of Life Sciences and Medicine University of Science and Technology of China 230026 Hefei Anhui Province China
3. Suzhou Institute for Advanced Research University of Science and Technology of China 215123 Suzhou China
Abstract
AbstractAmphiphilic 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), BPnbs‐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 BPnbs‐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 Fe2+ can catalyze intracellular hydrogen peroxide (H2O2) 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.