文献类型：期刊文献

英文题名：Photodynamic therapy synergizes with PD-L1 checkpoint blockade for immunotherapy of CRC by multifunctional nanoparticles

作者：Yuan, Zeting[1,3,4,5];Fan, Guohua[1,3];Wu, Honglei[1,3,6];Liu, Chaolian[1,3,4];Zhan, Yueping[1,3];Qiu, Yanyan[1,3];Shou, Chenting[4];Gao, Feng[4];Zhang, Jun[7];Yin, Peihao[1,3,5,6];Xu, Ke[2,3,5,8]

机构：[1]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai 200062, Peoples R China;[2]Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[5]Anhui Med Univ, Sch Clin Med, Shanghai Putuo Cent, Hefei 230032, Peoples R China;[6]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China;[7]Univ Kansas, Div Med Oncol, Dept Internal Med, Dept Canc Biol,Ctr Canc,Med Ctr, 3005 Wahl Hall East,3901 Rainbow Blvd, Kansas City, KS 66160 USA;[8]Shanghai Univ, Wenzhou Inst, Wenzhou 325000, Peoples R China

年份：2021

卷号：29

期号：10

起止页码：2931

外文期刊名：MOLECULAR THERAPY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000708324600009)】；

基金：Special thanks to Dr. Jie Wang and Dr. Teng Chen for the help during the study. This project was sponsored by the National Nature Science Foundation of China (81973700, 81873137), the Clinical Specialized Disease Construction Project of Shanghai Putuo District Municipal Health Comission (no. 2019tszb01), and the Shanghai Key Medical Specialty Construction Project (no. ZK2019B18).

语种：英文

摘要：Checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have been shown to be extraordinarily effective, but their dura-ble response rate remains low, especially in colorectal cancer (CRC). Recent studies have shown that photodynamic therapy (PDT) could effectively enhance PD-L1 blockade therapeutic effects, although the reason is still unclear. Here, we report the use of multifunctional nanoparticles (NPs) loaded with photosensitized mTHPC (mTHPC@VeC/T-RGD NPs)-medi-ated PDT treatment to potentiate the anti-tumor efficacy of PD-L1 blockade for CRC treatment and investigate the under-lying mechanisms of PDT enhancing PD-L1 blockade thera-peutic effect in this combination therapy. In this study, the mTHPC@VeC/T-RGD NPs under the 660-nm near infrared (NIR) laser could kill tumor cells by inducing apoptosis and/ or necrosis and stimulating systemic immune response, which could be further promoted by the PD-L1 blockade to inhibit primary and distant tumor growth, as well as building long-term host immunological memory to prevent tumor recur-rence. Furthermore, we detected that mTHPC@VeC/T-RGD NP-mediated PDT sensitizes tumors to PD-L1 blockade ther-apy mainly because PDT-mediated hypoxia could induce the hypoxia-inducible factor 1a (HIF-1a) signaling pathway that upregulates PD-L1 expression in CRC. Taken together, our work demonstrates that mTHPC@VeC/T-RGD NP-mediated PDT is a promising strategy that may potentiate the response rate of anti-PD-L1 checkpoint blockade immunotherapies in CRC.