Combined positron emission tomography‐guided modified black phosphorus nanosheet‐based photothermal therapy and anti programmed cell death protein ligand 1 therapy

Abstract

BackgroundPatients 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.MethodsBPNSs 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.ResultsBPNS@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.ConclusionsBPNS@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.