RBC-derived nanosystem with enhanced ferroptosis triggered by oxygen-boosted phototherapy for synergized tumor treatment

Photodynamic and ferroptosis therapies for cancer treatment are restricted by the scarcity of oxygen and Fe in cancer cells, and the complicated structure of delivery systems. Herein, a red blood cell-derived vehicle (RDV) inherently enriched with hemoglobin co-delivers a photosensitizer, Ce6, and a ferroptosis promoter, sorafenib (SRF) into cancer cells for boosting oxygen and providing iron, which leads to enhanced PDT and stronger ferroptosis therapy. Damage to the RDV membrane under local irradation leads to SRF release at the tumor site for tumor-targeted therapy. The lipid membrane of the RDV could also improve the drug delivery efficiency in vitro and in vivo. The novel nanosystem exhibited enhanced tumor killing efficacy and improved safety compared with traditional PDT and ferroptosis therapy.