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

Juliana Cano-Mejia; Rachel A Burga; Elizabeth E Sweeney; John P Fisher; Catherine M Bollard; Anthony D Sandler; Conrad Russell Y Cruz; Rohan Fernandes

doi:10.1016/j.nano.2016.10.015

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

Nanomedicine. 2017 Feb;13(2):771-781. doi: 10.1016/j.nano.2016.10.015. Epub 2016 Nov 5.

Authors

Juliana Cano-Mejia¹, Rachel A Burga², Elizabeth E Sweeney³, John P Fisher⁴, Catherine M Bollard⁵, Anthony D Sandler⁶, Conrad Russell Y Cruz⁷, Rohan Fernandes⁸

Affiliations

¹ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA. Electronic address: jcm22@terpmail.umd.edu.
² The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Institute for Biomedical Sciences, The George Washington University, DC, USA. Electronic address: RBurga@childrensnational.org.
³ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA. Electronic address: ESweeney@childrensnational.org.
⁴ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA. Electronic address: jpfisher@umd.edu.
⁵ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Institute for Biomedical Sciences, The George Washington University, DC, USA; Center for Cancer and Immunology Research, Washington, DC, USA; Department of Pediatrics, The George Washington University, DC, USA. Electronic address: CBollard@childrensnational.org.
⁶ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Institute for Biomedical Sciences, The George Washington University, DC, USA; Department of Pediatrics, The George Washington University, DC, USA; The Joseph E. Robert Jr. Center for Surgical Care, Children's National Health System, Washington, DC, USA. Electronic address: ASandler@childrensnational.org.
⁷ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Institute for Biomedical Sciences, The George Washington University, DC, USA; Center for Cancer and Immunology Research, Washington, DC, USA; Department of Pediatrics, The George Washington University, DC, USA. Electronic address: CCruz@childrensnational.org.
⁸ The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA; Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA; Institute for Biomedical Sciences, The George Washington University, DC, USA; Department of Pediatrics, The George Washington University, DC, USA; Department of Radiology, The George Washington University, DC, USA. Electronic address: RFernand@childrensnational.org.

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 100days 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.

Keywords: Checkpoint inhibitors; Immunotherapy; Neuroblastoma; Photothermal immunotherapy; Photothermal therapy; Prussian blue nanoparticles.

MeSH terms

Animals
CTLA-4 Antigen / immunology
Coloring Agents / chemistry
Immunotherapy / methods*
Mice
Nanomedicine
Nanoparticles*
Neuroblastoma / therapy*
Phototherapy*
T-Lymphocytes

Substances

CTLA-4 Antigen
Coloring Agents

Abstract

MeSH terms

Substances

Grants and funding