Background: Photodynamic therapy (PDT) is an effective therapeutic modality that has been extensively studied in treatment of various cancers. However, issues with inadequate oxygen (O₂) 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 CAT-Ce6@OMV-aPDL1 were evaluated systematically.
Results: The self-assembly nanocomplex (CAT-Ce6) generated sufficient O₂ 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 CAT-Ce6@OMV-aPDL1 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 memory effect, which inhibited tumor development efficiently.
Conclusion: The resultant CAT-Ce6@OMV-aPDL1 displays excellent efficacy of PDT and immunotherapy to achieve antitumor effects, which provides a new avenue for combinatorial therapy against various cancers.
Keywords: oxygenated photodynamic therapy, anti-tumor immune response, long term hypoxia relieving, immune memory effect