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Photothermal therapy mediated by phase-transformation nanoparticles facilitates delivery of anti-PD1 antibody and synergizes with antitumor immunotherapy for melanoma

Zhang, Ni, Song, Jiao, Liu, Yi, Liu, Mingzhu, Zhang, Liang, Sheng, Danli, Deng, Liming, Yi, Hengjing, Wu, Meng, Zheng, Yuanyi, Wang, Zhigang, Yang, Zhu
Journal of controlled release 2019 v.306 pp. 15-28
CD8-positive T-lymphocytes, antibodies, droplets, immunotherapy, melanoma, mice, nanocarriers, nanoparticles, particle size, peptides, photothermotherapy, remission, toxicity, volatilization
Melanoma remains one of the most challenging malignant tumor related deaths worldwide and alternative approaches to efficiently treat melanoma are eagerly needed. Anti-PD1 antibody (aPD1) immunotherapy is the most significant and impactful therapy for melanoma by immune checkpoint inhibition and T cell stimulation to mediate tumor killing. But the clinical remission rate of aPD1 immunotherapy is limited in melanoma. Here we show a potent combination of aPD1 and photothermal therapy (PTT) by effective delivery of a multifunctional phase-transformation nanocarrier to melanoma tumor. We successfully synthesized multifunctional nanoparticles (NPs) encapsulated with aPD1, iron oxide and perfluoropentane (PFP) in lactic-co-glycolic acid (PLGA) shell modified with poly ethylene glycol (PEG) and Gly-Arg-Gly-Asp-Ser (GRGDS) peptides (GOP@aPD1). In vitro, GOP@aPD1 NPs were characterized for particle size and drug-loading efficiency. The NPs were also tested for photothermal property, optical droplet vaporization (ODV) capacity and the ability of aPD1 release profile. In vivo, GOP@aPD1 NPs were systemically administered to melanoma-bearing mice demonstrated no toxicity and accumulation at tumor site. When mediated with PTT, this synergistic treatment achieved enhanced antitumor efficacy, due to combination of the effective aPD1 release and increased CD8+ T cell infiltration in tumor site. In conclusion, GOP@aPD1 NPs combined with PTT could potentiate the efficacy of aPD1 not only by tumor-targeted delivery of aPD1 but also by activating the immune system in the tumor microenvironment, which is a highly effective approach to treat melanoma.