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 (H 2 O 2 ) 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 DiIC 18 (5, DiD) and soravtansine ( [email?protected] ) 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, [email?protected] preferentially accumulated at tumor sites, flexibly penetrated into the interior regions of tumor mass and remarkably relieved the hypoxic status in tumor. Notably, the [email?protected] ?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.