Prussian blue nanoparticle-based photothermal therapy combined with checkpoint inhibition for photothermal immunotherapy of neuroblastoma

Abstract 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 su...

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Bibliographic Details
Published in:Nanomedicine 2017-02, Vol.13 (2), p.771-781
Main Authors: Cano-Mejia, Juliana, Burga, Rachel A, Sweeney, Elizabeth E, Fisher, John P, Bollard, Catherine M, Sandler, Anthony D, Cruz, Conrad Russell Y, Fernandes, Rohan
Format: Article
Language:English
Subjects:
Animals
Checkpoint inhibitors
Coloring Agents - chemistry
CTLA-4 Antigen - immunology
Immunotherapy
Immunotherapy - methods
Internal Medicine
Mice
Nanomedicine
Nanoparticles
Neuroblastoma
Neuroblastoma - therapy
Phototherapy
Photothermal immunotherapy
Photothermal therapy
Prussian blue nanoparticles
T-Lymphocytes
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Summary:Abstract 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.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2016.10.015