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

Nanomedicine (Lond). 2024;19(25):2049-2064. doi: 10.1080/17435889.2024.2389770. Epub 2024 Sep 3.

Abstract

Aim: 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.Methods: 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.Results: The αCD137-PBNPs retained both the photothermal and agonistic properties of the PBNPs and αCD137, respectively. In vivo, SM1 tumor-bearing mice treated with αCD137-PBNP-PTT exhibited a significantly higher survival rate (50%) without hepatotoxicity, compared with control treatments.Conclusion: These data suggest the potential utility of co-localizing PBNP-PTT with αCD137-based agonism as a novel combination nanomedicine.

Keywords: Prussian blue nanoparticles; anti-CD137; combination immunotherapy; melanoma; nanoimmunotherapy; photothermal therapy.

Plain language summary

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Ferrocyanides* / chemistry
  • Ferrocyanides* / pharmacology
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Melanoma / drug therapy
  • Melanoma / therapy
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / therapy
  • Mice
  • Nanoparticles* / chemistry
  • Photothermal Therapy* / methods
  • Tumor Necrosis Factor Receptor Superfamily, Member 9* / agonists

Substances

  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • ferric ferrocyanide
  • Ferrocyanides