Prussian blue nanoparticle-based photothermal therapy combined with checkpoint inhibition for photothermal immunotherapy of neuroblastoma.
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.
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.
Juliana
J
Cano-Mejia
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.
Rachel A
RA
Burga
The Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC, USA. Electronic address: ESweeney@childrensnational.org.
Elizabeth E
EE
Sweeney
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.
John P
JP
Fisher
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.
Catherine M
CM
Bollard
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.
Anthony D
AD
Sandler
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.
Conrad Russell Y
CRY
Cruz
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.
Rohan
R
Fernandes
D000818:Animals; D060908:CTLA-4 Antigen / Q000276:immunology; D004396:Coloring Agents / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles; D009447:Neuroblastoma / Q000628:therapy*; D010789:Phototherapy; D013601:T-Lymphocytes
D060908:CTLA-4 Antigen; D004396:Coloring Agents
Checkpoint inhibitors; Immunotherapy; Neuroblastoma; Photothermal immunotherapy; Photothermal therapy; Prussian blue nanoparticles