AIEgen-Loaded MnO ₂ Nanoparticles for Hypoxia Alleviation in Cancer Therapy

Cancer treatment remains a significant challenge due to the complex tumor microenvironment (TME) and hypoxic conditions, which significantly contribute to drug resistance. In this study, we report the development of a new multifunctional nanoparticle system exhibiting dual functionality for effective cancer therapy. The nanoplatform integrates a near-infrared aggregation-induced emission (AIE) luminogen 3T with oxygen-generating MnO2 nanoparticles to achieve simultaneous hypoxia relief and effective antiproliferative activity. An in vitro study demonstrated its excellent antiproliferative activity and the ability to generate oxygen in both monolayer cultures and tumor spheroids. The synthesized PEG-3T-MnO2 nanoparticles were able to generate 3.4-fold reactive oxygen species (ROS) and induced changes in the mitochondrial membrane potential, leading to induction of apoptosis. An increase in 40.4% apoptotic population was observed in the highly aggressive metastatic MDA-MB-231 cells after treatment. Further, Western blot analysis revealed a decrease in the expression of hypoxia-inducible factor-1α (HIF-1α). Overall, the PEG-3T-MnO2 nanoparticles represent an innovative approach to modulate the TME, a promising strategy by alleviating hypoxia and potentially improving overall treatment efficacy.