Self-oxygenated co-assembled biomimetic nanoplatform for enhanced photodynamic therapy in hypoxic tumor  

作　　者：Bingchen Zhang Ling Lin Jizong Mao Weisheng Mo Zibo Li Shengtao Wang Yan Tang Chunhui Cui Yifen Wu Zhiqiang Yu 

机构地区：[1]Department of Laboratory Medicine,Dongguan Institute of Clinical Cancer Research,Affiliated Dongguan Hospital,Southern Medical University,Dongguan 523058,China [2]Dongguan Institute of Clinical Cancer Research,Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors,Affiliated Dongguan Hospital,Southern Medical University,Dongguan 523058,China [3]Department of General Surgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China [4]Affiliated Foshan Maternity&Child Healthcare Hospital,Southern Medical University(Foshan Maternity&Child Healthcare Hospital),Foshan 528000,China

出　　处：《Chinese Chemical Letters》2023年第10期174-179,共6页中国化学快报（英文版）

基　　金：supported by the Guangdong Nature Resource Center(No.(2020)037);Natural Science Foundation of Guangdong Province(Nos.22019A1515011498 and 2019A1515011619);Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120063);National Natural Science Foundation of China(No.81803877);supported by the China Postdoctoral Science Foundation(No.2022M721535)。

摘　　要：Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.

关 键 词：Photodynamic therapy Biomimetic nanoplatform Self-oxygenated co-assembly nanoparticles Immunogenic cell death HIF-1α-CD39-CD73-A2AR pathway 

分 类 号：R73[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]