Photothermal therapy co-localized with CD137 agonism improves survival in an SM1 melanoma model without hepatotoxicity

<b>Aim:</b> We investigate combining Prussian Blue nanoparticles (PBNPs), as photothermal therapy (PTT) agents, with agonistic CD137 antibodies (αCD137) on a single nanoparticle platform to deliver non-toxic, anti-tumor efficacy in SM1 murine melanoma. <b>Methods:</b> We electrostatically coated PBNPs with αCD137 (αCD137-PBNPs) and quantified their physicochemical characteristics, photothermal and co-stimulatory capabilities. Next, we tested the efficacy and hepatotoxicity of PTT using αCD137-PBNPs (αCD137-PBNP-PTT) in SM1 tumor-bearing mice. <b>Results:</b> The αCD137-PBNPs retained both the photothermal and agonistic properties of the PBNPs and αCD137, respectively. <i>In vivo</i>, SM1 tumor-bearing mice treated with αCD137-PBNP-PTT exhibited a significantly higher survival rate (50%) without hepatotoxicity, compared with control treatments. <b>Conclusion:</b> These data suggest the potential utility of co-localizing PBNP-PTT with αCD137-based agonism as a novel combination nanomedicine. Photothermal therapy is a strategy to kill cancer cells that uses nanoparticles and lasers to generate heat. Here, we combine photothermal therapy with an immunotherapy that activates the body's T cells, a type of white blood cell, on a single platform, to treat melanoma, a type of skin cancer in a mouse. We find that this novel nanoparticle-based platform significantly improves the survival of mice bearing melanoma, without increasing liver toxicity. Agonistic antibodies targeting CD137 (αCD137) can be transiently coated onto Prussian blue nanoparticles (PBNPs; αCD137-PBNPs). αCD137-PBNPs function as effective PTT agents and heat SM1 murine melanoma cells in a dose-dependent manner. αCD137 retains agonistic function on αCD137-PBNPs as measured by sustained T cell activation <i>in vitro</i>. Photothermal therapy using αCD137-PBNPs (αCD137-PBNP-PTT) initiates similar changes in immunogenic markers on SM1 cells as PBNP-PTT. αCD137-PBNP-PTT effectively treats SM1 tumors <i>in vivo</i> by decreasing tumor growth and significantly improving mouse survival. αCD137-PBNP-PTT does not increase hepatotoxicity in treated mice.