A d-peptide-based oral nanotherapeutic modulates the PD-1/PD-L1 interaction for tumor immunotherapy

作者：Dan Liu, Jingmei Wang, Weiming You, Fang Ma, Qi Sun, Junjun She, Wangxiao He, Guang Yang · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1228581 · 被引用次数：9 · 研究领域：Extracellular vesicles in disease、Immunotherapy and Immune Responses、Nanoplatforms for cancer theranostics

Background PD-1/PD-L1 immune checkpoint inhibitors are currently the most commonly utilized agents in clinical practice, which elicit an immunostimulatory response to combat malignancies. However, all these inhibitors are currently administered via injection using antibody-based therapies, while there is a growing need for oral alternatives. Methods This study has developed and synthesized exosome-wrapped gold–peptide nanocomplexes with low immunogenicity, which can target PD-L1 and activate antitumor immunity in vivo through oral absorption. The Super PDL1 exo was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel silver staining. The transmembrane ability of Super PDL1 exo was evaluated by flow cytometry and immunofluorescence. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. ELISA experiments were conducted to detect serum and tissue inflammatory factors, as well as serum biochemical indicators. Tissue sections were stained with H&E for the evaluation of the safety of Super PDL1 exo . An MC38 colon cancer model was established in immunocompetent C56BL/6 mice to evaluate the effects of Super PDL1 exo on tumor growth in vivo . Immunohistochemistry (IHC) staining was performed to detect cytotoxicity factors such as perforin and granzymes. Results First, Super PDL1 was successfully synthesized, and milk exosome membranes wer...