Phospholipid membrane-decorated deep-penetrated nanocatalase relieve tumor hypoxia to enhance chemo-photodynamic therapy

摘要

Hypoxia is a serious impediment to current treatments of many malignant tumors. Catalase, an antioxidant enzyme, is capable of decomposing endogenous hydrogen peroxide (H2O2) into oxygen for tumor reoxygenation, but suffered from in vivo instability and limited delivery to deep interior hypoxic regions in tumor. Herein, a deep-penetrated nanocatalase-loading DiIC18 (5, DiD) and soravtansine (Cat@PDS) were provided by coating catalase nanoparticles with PEGylated phospholipids membrane, stimulating the structure and function of erythrocytes to relieve tumor hypoxia for enhanced chemo-photodynamic therapy. After intravenous administration, Cat@PDS preferentially accumulated at tumor sites, flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in tumor. Notably, the Cat@PDS + laser treatment produced striking inhibition of tumor growth and resulted in a 97.2% suppression of lung metastasis. Thus, the phospholipids membrane-coated nanocatalase system represents an encouraging nanoplatform to relieve tumor hypoxia and synergize the chemo-photodynamic cancer therapy.