Title

Interstitial Photothermal Therapy Generates Durable Treatment Responses in Neuroblastoma

Authors

Debbie K. Ledezma, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Preethi B. Balakrishnan, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Anshi Shukla, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Jacob A. Medina, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Jie Chen, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Emily Oakley, Photodynamic Therapy Center, Roswell Park Comprehensive Cancer Center, Department of Cell Stress Biology, Roswell Park, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
Catherine M. Bollard, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.
Gal Shafirstein, Photodynamic Therapy Center, Roswell Park Comprehensive Cancer Center, Department of Cell Stress Biology, Roswell Park, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
Mario Miscuglio, Department of Electrical and Computer Engineering, The George Washington University, 800 22nd St NW, 5000 Science and Engineering Hall, Washington, DC, 20052, USA.
Rohan Fernandes, The George Washington Cancer Center, The George Washington University, 800 22nd St NW, 8300 Science and Engineering Hall, Washington, DC, 20052, USA.

Document Type

Journal Article

Publication Date

8-9-2022

Journal

Advanced healthcare materials

DOI

10.1002/adhm.202201084

Keywords

Prussian blue nanoparticles; diffuser; interstitial laser; neuroblastoma; photothermal therapy; thermal dose

Abstract

Photothermal therapy (PTT) represents a promising modality for tumor control typically using infrared light-responsive nanoparticles illuminated by a wavelength-matched external laser. However, due to the constraints of light penetration, PTT is generally restricted to superficially accessible tumors. With the goal of extending the benefits of PTT to all tumor settings, interstitial PTT (I-PTT) is evaluated by the photothermal activation of intratumorally administered Prussian blue nanoparticles with a laser fiber positioned interstitially within the tumor. This interstitial fiber, which is fitted with a terminal diffuser, distributes light within the tumor microenvironment from the "inside-out" as compared to from the "outside-in" traditionally observed during superficially administered PTT (S-PTT). I-PTT improves the heating efficiency and heat distribution within a target treatment area compared to S-PTT. Additionally, I-PTT generates increased cytotoxicity and thermal damage at equivalent thermal doses, and elicits immunogenic cell death at lower thermal doses in targeted neuroblastoma tumor cells compared to S-PTT. In vivo, I-PTT induces significantly higher long-term tumor regression, lower rates of tumor recurrence, and improved long-term survival in multiple syngeneic murine models of neuroblastoma. This study highlights the significantly enhanced therapeutic benefit of I-PTT compared to traditional S-PTT as a promising treatment modality for solid tumors.

Department

Medicine

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