Engineered Enzyme-Loaded Erythrocyte Vesicles Precisely Deprive Tumoral Nutrients to Induce Synergistic Near-Infrared-II Photothermal Therapy and Immune Activation

作者：Nie, Chengtao; Pan, Weilun; Wu, Bodeng; Luo, Tingting; Lv, Jie; Fan, Yingjing; Feng, Junjie; Liu, Chunchen; Guo, Jingyun; Li, Bo^*; Bai, Xiaochun^*; Zheng, Lei^*

来源：ACS Nano, 2023, 17(14): 13211-13223.

DOI：10.1021/acsnano.3c00345

• starvation therapy
• enzyme-loaded
• engineerederythrocyte vesicle
• tumor microenvironment
• NIR-IIphotothermal therapy
• immune activation

Starvationtherapy has been considered a promising strategy incancer treatment for altering the tumor microenvironment (TME) andcausing a cascade of therapeutic effects. However, it is still highlychallenging to establish a therapeutic strategy for precisely andpotently depriving tumoral nutrition. In this study, a glucose oxidase(GOx) and thrombin-incorporated erythrocyte vesicle (EV) with cyclic(Arg-Gly-Asp) (cRGD) peptide modification, denoted as EV@RGT, weresynthesized for precisely depriving tumoral nutrition and sequentiallyinducing second near-infrared region (NIR-II) photothermal therapy(PTT) and immune activation. The EV@RGT could specifically accumulateat the tumor site and release the enzymes at the acidic TME. The combinationof GOx and thrombin exhausts tumoral glucose and blocks the nutritionsupply at the same time, resulting in severe energy deficiency andreactive oxygen species (ROS) enrichment within tumor cells. Subsequently,the abundant clotted erythrocytes in tumor vessels present outstandinglocalized NIR-II PTT for cancer eradication owing to the hemoglobin.Furthermore, the abundant ROS generated by enhanced starvation therapyrepolarizes resident macrophages into the antitumor M1 phenotype viaa DNA damage-induced STING/NF-& kappa;B pathway, ultimately contributingto tumor elimination. Consequently, the engineered EV@RGT demonstrates powerful antitumor efficiency based on precise nutrition deprivation, sequential NIR-II PTT, and immune activation effect. This work providesan effective strategy for the antitumor application of enzyme-basedreinforced starvation therapy.

• 单位
  南方医科大学