Abstract
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
Highlights
Immunotherapy is a novel strategy for tumor therapy that works via an activated immune system [1,2,3]
The morphology and particle size of antigen–antibody integrator (AAI) were studied by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively; the results showed that the morphology was the same as that of aPD-L1 NVs (Fig. 5b, c)
AAI-R837 triggered the highest level of CD11c + CD86 + expression relative to free R837, NVs-R837, and free OVA; its strongest stimulation ability was with dendritic cells (DCs). These results show that AAI-R837 displaying aPD-L1 can bind to bone marrow-derived DCs (BMDCs) and can deliver the immunologic adjuvant and tumor-related antigens (TAAs) to BMDCs, significantly enhancing their differentiation
Summary
Immunotherapy is a novel strategy for tumor therapy that works via an activated immune system [1,2,3]. The tumor microenvironment is immunosuppressive, and conventional delivery of immune adjuvants and tumor-related antigens (TAAs) cannot effectively activate the tumor immune response [4,5,6]. TAAs or immunogenic fragments of cancer cells released during tumor apoptosis can be phagocytosed by infiltrating antigen presenting cells (APCs); this in turn can activate the body’s immune response to the tumor [8, 9]. A versatile nanoplatform to selectively deliver photosensitizers or adjuvants to target specific cell populations and tumor tissues while overcoming the above-mentioned challenges would have significant value. Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. 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
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