<p>Multifunctional Immunoliposomes Combining Catalase and PD-L1 Antibodies Overcome Tumor Hypoxia and Enhance Immunotherapeutic Effects Against Melanoma</p>
Yu Hei, Binhong Teng, Ziqian Zeng, SiQi Zhang, Qian Li, Jijia Pan, Zuyuan Luo, Chunyang Xiong, Shicheng Wei
Abstract
Background: Immune checkpoint blockades (ICBs) are a promising treatment for cancers such as melanoma by blocking important inhibitory pathways that enable tumor cells to evade immune attack. Programmed death ligand 1 monoclonal antibodies (aPDL1s) can be used as an ICB to significantly enhance the effectiveness of tumor immunotherapy by blocking the PD-1/PD-L1 inhibitory pathway. However, the effectiveness of aPDL1s may be limited by low selectivity in vivo and immunosuppressed tumor microenvironment including hypoxia. Purpose: To overcome the limitations, we develop a multifunctional immunoliposome, called [email protected] , with catalase (CAT) encapsulated inside to overcome tumor hypoxia and aPDL1s modified on the surface to enhance immunotherapeutic effects against melanoma. Methods: The multifunctional immunoliposomes ( [email protected] ) are prepared using the film dispersion/post-insertion method. The efficacy of [email protected] is verified by multiple experiments in vivo and in vitro. Results: The results of this study suggest that the multifunctional immunoliposomes preserve and protect the enzyme activity of CAT and ameliorate tumor hypoxia. Moreover, the enhanced cellular uptake of [email protected] in vitro and their in vivo biodistribution suggest that [email protected] have great targeting ability,resulting in improved delivery and accumulation of immunoliposomes in tumor tissue.Finally, by activating and increasing the infiltration of CD8 + T cells at the tumor site, [email protected] inhibit the growth of tumor and prolong survival time of mice,with low systemic toxicity. Conclusion: In conclusion, the multifunctional immunoliposomes developed and proposed in this study are a promising candidate for melanoma immunotherapy, and could potentially be combined with other cancer therapies like radiotherapy and chemotherapy to produce positive outcomes. Keywords: immunotherapy, programmed death ligand 1 monoclonal antibodies, aPDL1s, tumor hypoxia, melanoma, liposomes