Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy

Journal of Nanobiotechnology

Yesi Shi¹  Chao Liu¹  Hu Chen¹  Qixuan Dai¹  Gang Liu¹  Yun Zeng¹  Hongwei Cheng¹  Xing Gao¹  Xiaoyong Wang¹  Pengfei Zhang²  Qianqian Zhou³ 

[1] State Key Laboratory of Molecular Vaccinology and Molecular, Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 361102, Xiamen, China;State Key Laboratory of Molecular Vaccinology and Molecular, Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 361102, Xiamen, China;Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, 510080, Guangzhou, China;Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 200336, Shanghai, China;

关键词: Photoimmunotherapy;    Anti-PD-L1 antibodies;    Targeting delivery;    Nanovesicles;   

DOI  :  10.1186/s12951-022-01266-3

来源: Springer

【 摘 要 】

BackgroundPhotoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery.ResultsThe high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen–antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions.ConclusionsaPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.Graphic Abstract

【 授权许可】

CC BY