A redox-triggered C-centered free radicals nanogenerator for self-enhanced magnetic resonance imaging and chemodynamic therapy

Current chemodynamic therapy (CDT) has been restricted by the requirement of strongly acidic conditions, insufficient endogenous H2O2 and upregulated cellular antioxidant defense. To overcome these obstacles, the carrier-free Fe(III)-ART nanoparticle is developed via coordination driven self-assembly of Fe3+ and hydrolyzed ART and evaluated as a redox-triggered C-centered free radicals nanogenerator for self-enhanced magnetic resonance imaging and chemodynamic therapy. The carrier-free Fe(III)-ART NPs can be triggered by intracellular GSH to release ART and Fe3+, which is further reduced to Fe2+ that catalyzed the endoperoxide of ART to generate C-centered free radicals. Notably, unlike current CDT, such a free radical generation process is without reliance on pH or endogenous H2O2. Meanwhile, the concurrent GSH depletion can diminish the antioxidation of tumors and enhance CDT. The C-centered free radicals-mediated apoptosis and GSH depletion-induced ferrotosis act in synergy, leading to potent tumor growth inhibition and superior anticancer efficacy in vitro and in vivo. Moreover, Fe(III)-ART NPs exhibit redox-triggered T2 relaxivity and contribute to activatable MRI-guided CDT. The development of biodegradable Fe(III)-ART NPs with superior anticancer efficacy, favorable pharmacokinetics and good biocompatibility provides a promising strategy to break through the bottlenecks of traditional CDT and greatly promotes the development of next-generation cancer theranostics.