Spatiotemporal Concurrent PARP Inhibitor Sensitization based on Radiation-Responsive Nanovesicles for Lung Cancer Chemoradiotherapy.

The implementation of chemoradiation combinations has gained great momentum in clinical practices. However, the full utility of this paradigm is often restricted by the discordant tempos of action of chemotherapy and radiotherapy. Here, we developed a gold nanoparticle-based radiation-responsive nanovesicle system loaded with cisplatin and veliparib, denoted as CV-Au NVs, to augment the concurrent chemoradiation effect in a spatiotemporally controllable manner of drug release. Upon irradiation, the in-situ generation of •OH induces the oxidation of polyphenylene sulfide from being hydrophobic to hydrophilic, resulting in the disintegration of the nanovesicles and the rapid release of the entrapped cisplatin and Veliparib (the PARP inhibitor). Cisplatin-induced DNA damage and the impairment of the DNA repair mechanism mediated by veliparib synergistically elicited potent pro-apoptotic effects. In vivo studies suggested that one-dose injection of the CV-Au NVs and one-time X-ray irradiation paradigm effectively inhibited tumor growth in A549 lung cancer model. This study provides new insight into designing nanomedicine platforms in chemoradiation therapy from a vantage point of synergizing both chemotherapy and radiation therapy in a spatiotemporally concurrent manner. This article is protected by copyright. All rights reserved.