Biomimetic Self-Oxygenated Immunoliposome for Cancer-Targeted Photodynamic Immunotherapy

Yucheng Tang,1– 3,* Tiantian Tang,1– 3,* Yongjiang Li,1– 3 Junyong Wu,1– 3 Xinyi Liu,1– 3 Daxiong Xiang,1– 3 Xiongbin Hu1– 3 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, 410011, People’s Republic of China; 3Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiongbin Hu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China, Email [email protected]: Photodynamic therapy (PDT) is a promising strategy with significant clinical application potential for tumor treatment. However, the tumor hypoxia and limited efficacy against tumor metastasis present significant limitations in the clinical application of PDT. To alleviate tumor hypoxia for PDT against tumor growth and metastasis, we developed a self-oxygenated immunoliposome by encapsulating the catalase (CAT) within the liposome cavity and loading the photosensitizer chlorin e6 (Ce6) and immunoadjuvant MPLA in the lipid bilayer of the immunoliposome (CAT@LP-Ce6-A). Subsequently, we fused it with the cancer cell membrane (CCM) to create the hybrid immunoliposome (CAT@LP-CCM-Ce6-A). The in vitro and in vivo anti-cancer efficacy of CAT@LP-CCM-Ce6-A-based photodynamic immunotherapy (PDIT) was evaluated.Methods: CAT@LP-CCM-Ce6-A were characterized by size, zeta potential, transmission electron microscopy (TEM), Coomassie bright blue staining, UV spectrophotometer, and standard Goth’s method. Cellular uptake, cell viability, reactive oxygen species (1O2) generation, calreticulin exposure, and ability to promote BMDCs maturation of CAT@LP-CCM-Ce6-A were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy, and in vivo safety of CAT@LP-CCM-Ce6-A were investigated in orthotopic triple-negative breast cancer (TNBC) lung metastasis mouse models.Results: CAT@LP-CCM-Ce6-A was successfully developed via the thin film hydration and co-extrusion method. The loading capacity of Ce6 and CAT was 4.7 ± 0.9% and 8.5 ± 0.9% respectively. CAT@LP-CCM-Ce6-A exhibited improved cellular uptake efficiency and cytotoxicity under laser irradiation against TNBC. Furthermore, CAT@LP-CCM-Ce6-A possessed enhanced anti-enzymatic degradation ability and promotion of DC maturation. In TNBC-bearing mice, CAT@LP-CCM-Ce6-A-based PDIT demonstrated remarkable therapeutic effect and antitumor immunity while maintaining minimal systemic toxicity.Conclusion: CAT@LP-CCM-Ce6-A could be employed as an innovative approach for self-oxygenated photodynamic immunotherapy against cancer.Keywords: liposome, photodynamic therapy, cancer, biomimetic