Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 2, Pages 771-781Publisher
ELSEVIER
DOI: 10.1016/j.nano.2016.10.015
Keywords
Prussian blue nanoparticles; Photothermal therapy; Checkpoint inhibitors; Immunotherapy; Photothermal immunotherapy; Neuroblastoma
Funding
- Sheikh Zayed Institute for Pediatric Surgical Innovation at Children's National Health System [RAC 30000161]
- The Louis Stokes Alliances for Minority Participation Program Fellowship [0833018]
- NIH National Center for Advancing Translational Sciences [UL1TR000075, KL2TR000076]
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We describe photothermal immunotherapy, which combines Prussian blue nanoparticle (PBNP)-based photothermal therapy (PTT) with anti-CTLA-4 checkpoint inhibition for treating neuroblastoma, a common, hard-to-treat pediatric cancer. PBNPs exhibit pH-dependent stability, which makes them suitable for intratumorally-administered PTT. PBNP-based PTT is able to lower tumor burden and prime an immune response, specifically an increased infiltration of lymphocytes and T cells to the tumor area, which is complemented by the antitumor effects of anti-CTLA-4 immunotherapy, providing a more durable treatment against neuroblastoma in an animal model. We observe 55.5% survival in photothermal immunotherapy-treated mice at 100 days compared to 12.5%, 0%, 0%, and 0% survival in mice receiving: anti-CTLA-4 alone, PBNPs alone, PTT alone, and no treatment, respectively. Additionally, long-term surviving, photothermal immunotherapy-treated mice exhibit protection against neuroblastoma rechallenge, suggesting the development of immunity against these tumors. Our findings suggest the potential of photothermal immunotherapy in improving treatments for neuroblastoma. (C) 2016 Elsevier Inc. All rights reserved.
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