机构:[1]State Key Laboratory of Molecular Vaccinology and Molecular, Diagnostics& Center for Molecular Imaging and Translational Medicine, School of PublicHealth, Xiamen University, Xiamen 361102, China[2]Institute of MolecularImmunology, School of Laboratory Medicine and Biotechnology, SouthernMedical University, Guangzhou 510080, China[3]Tongren Hospital, ShanghaiJiao Tong University School of Medicine, Shanghai 200336, China
Background: Photoimmunotherapy 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. Results: The 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. Conclusions: aPD-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.
基金:
National Natural Science Foundation of China
(U1705281, 81925019, 81422023, 81871404, 81860386 and 81603015), the
National Key Research and Development Program of China (2017YFA0205201
and 2018YFC1105900), China Postdoctoral Science Foundation (2020TQ0181
and 2021M690096), the Fundamental Research Funds for the Central Universities
(20720190088 and 2020Y4003), and the Program for New Century Excellent
Talents in University, China (NCET-13–0502).
第一作者机构:[1]State Key Laboratory of Molecular Vaccinology and Molecular, Diagnostics& Center for Molecular Imaging and Translational Medicine, School of PublicHealth, Xiamen University, Xiamen 361102, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Hu Chen,Pengfei Zhang,Yesi Shi,et al.Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy[J].JOURNAL OF NANOBIOTECHNOLOGY.2022,20(1):doi:10.1186/s12951-022-01266-3.
APA:
Hu Chen,Pengfei Zhang,Yesi Shi,Chao Liu,Qianqian Zhou...&Gang Liu.(2022).Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy.JOURNAL OF NANOBIOTECHNOLOGY,20,(1)
MLA:
Hu Chen,et al."Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy".JOURNAL OF NANOBIOTECHNOLOGY 20..1(2022)