摘要
Background:Patients with cold tumors gain limited benefits from immune checkpoint blockade(ICB)therapy owing to low programmed cell death protein ligand 1(PD-L1)expression and minimal immune cell infiltration.Mild photothermal therapy(PTT)using black phosphorus nanosheets(BPNSs)is a promising approach to enhance the efficacy of ICB therapy.However,to ensure that BPNS-based PTT-enhanced ICB therapy is clinically adaptable,a noninvasive,bedside-accessible imaging tool capable of monitoring the status of PD-L1 is imperative.We demonstrated that positron emission tomography(PET)using[64Cu]HKP2202 precisely delineated PD-L1 expression in tumors receiving PTT.Methods:BPNSs were modified with polyethylene glycol to prepare BPNS@PEG,which were then characterized.MC38 cells and tumor allografts were treated with BPNS@PEG followed by 808 nm near-infrared light expo-sure.PET using[64Cu]HKP2202 was performed to monitor PD-L1 expression in vivo.We also evaluated whether the efficacy of ICB therapy improved after delivering BPNS@PEG-based PTT.Results:BPNS@PEG had a well-defined lamellar structure with clear edges and an average size of 150 nm.PET and Western blotting assays indicated that PD-L1 expression was upregulated after BPNS@PEG and NIR-light treatment.Notably,the antitumor effect of anti PD-L1 therapy was enhanced in mice treated with BPNS@PEG-based PTT.Conclusions:BPNS@PEG had the capacity to convert cold tumors into hot tumors to facilitate the efficacy of ICB therapy.Importantly,the comple-mentary diagnostic PET radiotracer targeting PD-L1 allowed real-time moni-toring of PD-L1 expression in the tumor microenvironment to guide ICB administration,holding great potential to achieve efficient and precise tumor immunotherapy.
基金
National Natural Science Foundation of China,Grant/Award Number:82372002
Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2022-RC350-04
CAMS Innovation Fund for Medical Sciences,Grant/Award Numbers:2021-I2M-1-026,2022-I2M-2-002-2,2021-I2M-3-001
National Key Research and Development Program of China,Grant/Award Number:2022YFE0111700
Beijing Nova Program awarded to K.H.,Grant/Award Number:0104002
Beijing Natural Science Foundation,Grant/Award Number:L234044
Fundamental Research Funds for the Central Universities,Grant/Award Numbers:3332023044,3332023151
CIRP Open Fund of Radiation Protection Laboratories
“Technological innovation”special project of CNNC Medical Industry Co.Ltd,Grant/Award Number:ZHYLYB2021005
China National Nuclear Corporation Young Talent Program。
