Combined positron emission tomography‐guided modified black phosphorus nanosheet‐based photothermal therapy and anti programmed cell death protein ligand 1 therapy
Xiaona Sun,
Siqi Zhang,
Shuo Jiang,
Jieting Shen,
Yuxuan Wu,
Hailong Zhang,
Ming‐Rong Zhang,
Rui Wang,
Kuan Hu
Affiliations
Xiaona Sun
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Siqi Zhang
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Shuo Jiang
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Jieting Shen
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Yuxuan Wu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Hailong Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences & Research Unit of Peptide Science Chinese Academy of Medical Sciences Lanzhou University Lanzhou Gansu Province China
Ming‐Rong Zhang
Department of Advanced Nuclear Medicine Sciences Institute of Quantum Medical Science National Institutes for Quantum Science and Technology Chiba Japan
Rui Wang
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Kuan Hu
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
Abstract 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 exposure. 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 complementary diagnostic PET radiotracer targeting PD‐L1 allowed real‐time monitoring of PD‐L1 expression in the tumor microenvironment to guide ICB administration, holding great potential to achieve efficient and precise tumor immunotherapy.
