Self-Assembly Catalase Nanocomplex Conveyed by Bacterial Vesicles for Oxygenated Photodynamic Therapy and Tumor Immunotherapy

作者：Jiayu Zhang, Zinan Li, Ling Liu, Longyun Li, Lu Zhang, Yongkun Wang, Jia Zhao · 发表于：International Journal of Nanomedicine · 年份：2022 · DOI：10.2147/ijn.s353330 · 被引用次数：40 · 研究领域：Nanoplatforms for cancer theranostics、Cancer Research and Treatments、Photodynamic Therapy Research Studies

Background: Photodynamic therapy (PDT) is an effective therapeutic modality that has been extensively studied in treatment of various cancers. However, issues with inadequate oxygen (O 2 ) concentration in tumor tissue and inadequate immune response generation have hindered its successful application in tumor therapy. Methods: Firstly, the self-assembly nanocomplex (CAT-Ce6), which is composed of hydrophilic catalase and hydrophobic photosensitizer Chlorin e6 (Ce6), was fabricated to support oxygenated PDT. Secondly, for supplying PDT with enhanced antitumoral immunity, CAT-Ce6 was coated with PD-L1 antibody modified-attenuated Salmonella outer membrane vesicles (OMV-aPDL1). Finally, the catalytic activity, tumor targeting, hypoxia ameliorating, immune effect initiating and anti-tumor capacities of the integral nanosystem [email protected] were evaluated systematically. Results: The self-assembly nanocomplex (CAT-Ce6) generated sufficient O 2 and promoted the solubility of Ce6 simultaneously, which enhanced PDT significantly. OMV-aPDL1 inherited most of the immunogenic membrane-associated components from the parent bacteria, possessing immunomodulation ability for immunosuppressive tumor microenvironment reprogramming and reducing immune escape. The obtained nanosystem [email protected] durably relieved hypoxia, resulting in amplifying PDT-mediated cytotoxicity to generate a pool of tumor-associated antigens, stimulating anti-tumor immune responses and even inducing an immune...