MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases  

作　　者：Changqiang Wu Wei Chen Shuang Yan Jie Zhong Liang Du Chenwu Yang Yu Pu Yang Li Jiafu Lin Mei Zeng Xiaoming Zhang 

机构地区：[1]Medical Imaging Key Laboratory of Sichuan Province and School of Medical Imaging,North Sichuan Medical College,Nanchong 637000,P.R.China [2]Department of Radiology,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,P.R.China [3]Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of Pharmacy,Chengdu University,Chengdu 610106,P.R.China [4]Institute of Basic Medicine and Forensic Medicine,North Sichuan Medical College and Institute of Rheumatology and Immunology,The Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,P.R.China

出　　处：《Regenerative Biomaterials》2024年第4期38-51,共14页再生生物材料（英文版）

基　　金：supported by National Natural Science Foundation of China[grant number 81601490];Natural Science Foundation of Sichuan Province[grant number 2022NSFSC0636];Science and Technology Project of Municipal School Strategic Cooperation,Nanchong[grant number 20SXQT0306];Pre-research Project of North Sichuan Medical College[grant number CBY19-YZ05];Open Research Program of Antibiotic Research and Reevaluation Key Laboratory of Sichuan Province[grant number ARRLKF20-03];Scientific Research Start-up Fund of North Sichuan Medical College[grant number CBY22-QDA03].

摘　　要：Non-invasive image-guided precise photothermal/photodynamic therapy(PTT/PDT)has been proven to be an effective local treatment modality but incompetent against metastases.Hence,the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication.Herein,a magnetic resonance imaging(MRI)-visualized PTT/PDT agent(SIDP NMs)was constructed,and the efficacy of its multimodal combination with a programmed cell death 1(PD-1)inhibitor in the treatment of melanoma and metastases was studied.Due to the hydrophobic encapsulation of indocyanine green within the micellar core,SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser.In vitro cell experiments showed that SIDP NMs had a good killing effect.After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min,cell viability decreased significantly.Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs.When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI,the temperature of the tumor area rapidly increased from 32℃to 60.7℃in 5 min.In mouse melanoma ablation and distant tumor immunotherapy studies,SIDP NMs provided excellent MRI-guided PTT/PDT results and,when combined with PD-1 inhibitor,have great potential to cure primary tumors and eradicate metastases.

关 键 词：photothermal therapy photodynamic therapy IMMUNOTHERAPY magnetic resonance imaging multimodal treatment 

分 类 号：R73-37[医药卫生—肿瘤]