Facile Synthesis of Near-Infrared Responsive On-Demand Oxygen Releasing Nanoplatform for Precise MRI-Guided Theranostics of Hypoxia-Induced Tumor Chemoresistance and Metastasis in Triple Negative Breast Cancer

Abstract Background：Hypoxia is an important factor that contributes to chemoresistance and metastasis, and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion.Methods: Herein, a near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. we embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation.Results: When guided with MRI, the dynamic accumulation of the nanosystem and the improvement of hypoxia in the tumor was monitored in real-time and quantitatively analyzed. The on-demand drug and oxygen release were achieved with NIR-induced photothermal effects to realize precise treatment for tumors via the overproduction of 1O2 and reactive oxygen species (ROS) as well as synergistic chemotherapy, photothermal, and hypoxia mitigation. There were no toxic side effects in major organs. More importantly, NIR-triggered nanomedicine could undermine the migration and invasion ability in the tumor via inhibiting the natural process of epithelial-mesenchymal transition.Conclusions: All in all, our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in triple negative breast cancer.