X-ray stimulates NQO1-dependent cascade reactions to induce strong immunogenicity for MRI-guided cancer radio-chemodynamic-immunotherapy
He Li, Jiaojiao Ma, Yiqun Wu, Chenguang Wang, Lan Tong, Lu Su, Lin Zhu, Shi-Wen Huang, Kai Deng, Yongchang Wei
Abstract
Background: Immunogenicity activation is vital for radioimmunotherapy, but the short-term oxidative damage caused by precise radiation planning limits this effect.Chemodynamic therapy (CDT) with prolonged generation of hydroxyl radical (OH) can initiate immunogenicity in combination with X-rays, however, its performance is constrained by tumor insufficient H2O2.Methods: Here, we propose to construct -lapachone-based nanoparticles (-Lap/Fe NPs) which initiate cascade reactions to generate high levels OH for an extended period in tumor following X-ray irradiation.Results: -Lap/Fe NPs, constructed by co-encapsulation of -Lap and Fe3O4 nanoparticles in reactive oxygen species (ROS) responsive C16-S-mPEG2000 micelles, remain stable under normal conditions but rapid decompose and release -Lap and Fe2+ when exposed to high level ROS.Upon X-ray irradiation, the upregulation of ROS and NAD (P) H: quinone oxidoreductase-1 (NQO1) in tumor cells accurately triggers -Lap/Fe NPs to persistently generate high levels H2O2 and OH for 12 hours, ultimately causing strong immunogenic cell death effects.Moreover, -Lap/Fe NPs with excellent T2-weighted magnetic resonance imaging provide imaging reference for guiding precise X-ray radiation and predicting OH generation.-Lap/Fe NPs mediated radio-chemodynamic-immunotherapy remarkably against primary tumor growth, and further shows effective suppression on untreated distant tumors via the abscopal effect.Conclusions: In a word, this work proposed the simple but powerful strategy for cancer radio-chemodynamic-immunotherapy that combines X-ray and CDT to remote locally and visually actuated long-time production of H2O2 and subsequently persistent generation of OH for initiating strong antitumor immune responses.