Fabrication of hypoxia-responsive and uperconversion nanoparticles-modified RBC micro-vehicles for oxygen delivery and chemotherapy enhancement

Abstract

Solid tumor cells in hypoxic regions resist chemotherapy treatment with conventional antitumor drugs (such as paclitaxel, PTX) because the inadequate O₂ attenuates the intracellular generation of reactive oxygen species (ROS) and upregulates multidrug resistance protein expression. Hyperbaric O₂ therapy concentrates on improving O₂ delivery to the hypoxic tumor area, thereby enhancing the sensitivity of cancer cells to chemotherapy drugs. However, the implementation of this therapy often elicits immune response or potentiates toxicity of the drugs toward normal cells. In this work, we successfully fabricated RBC-based micro-vehicles for precise hypoxia-activated O₂ delivery under the 980 nm laser irradiation. Interestingly, the subsequent chemotherapy of PTX for ovarian tumors was significantly enhanced owing to the alleviation of hypoxia tumor microenvironment. Meanwhile, the RBC-based micro-vehicles have low side tissue effects, superior biocompatibility, and ultra-low immune response. Overall, the RBC-based drug delivery system holds a fascinating perspective towards O₂ delivery for chemotherapy enhancement in other clinical solid malignancies.