A cyclic nano-reactor achieving enhanced photodynamic tumor therapy by reversing multiple resistances

Journal of Nanobiotechnology

Surong Hua¹  Yong Li²  Xinyi Shi³  Peng Liu³  Yu Yuan³  Ying Peng³  Jinsong Ding³  Wenhu Zhou³  Yanbin Zhou³  Qiange Luo³ 

[1] Department of General Surgery, Peking Union Medical College Hospital, 100730, Beijing, China;Department of Pediatric Surgery, Hunan Children’s Hospital, 410004, Changsha, Hunan, China;Xiangya School of Pharmaceutical Sciences, Central South University, 410013, Changsha, Hunan, China;

关键词: Nanomedicine;    Targeting;    Tumor hypoxia;    Drug resistance;    Starvation therapy;    GSH depletion;    Oxygenation;    Metal–organic-frameworks;   

DOI  :  10.1186/s12951-021-00893-6

来源: Springer

【 摘 要 】

BackgroundPhotodynamic therapy (PDT) is a clinically implemented modality to combat malignant tumor, while its efficacy is largely limited by several resistance factors from tumor microenvironment (TME), such as hypoxia, anti-oxidant systems, and ATP-dependent tumor adaptive resistances. The aim of this work is to construct a multifunctional nanoplatform to remodel multiple resistant TME for enhanced PDT.ResultsHere, a targeting nano-reactor was facilely constructed to reverse the multiple resistances of PDT by incorporating glucose oxidase (GOx) and chlorin e6 (Ce6) into poly (D, L-lactic-co-glycolic acid) (PLGA)/ metal–organic framework (MOF) core–shell nanoassembly, with surface deposition of hyaluronic acid (HA) stabilized MnO2. The nano-reactor could selectively target tumor cells by virtue of surface HA modification, and once internalization, a few reactions were initiated to modulate TME. Glucose was consumed by GOx to inhibit ATP generation, and the produced H2O2 was catalyzed by MnO2 to generate O2 for tumor hypoxia alleviation and photodynamic sensitization, and glutathione (GSH) was also effectively depleted by MnO2 to suppress the tumor antioxidant defense. Consequently, the nano-reactor achieved robust PDT with amplified tumor therapy via intravenous injection.ConclusionsThis nano-reactor offers a multifunctional nanoplatform to sensitize TME-limited tumor treatment means via reversing multiple resistances.Grpahic abstract

【 授权许可】

CC BY