Anti-Fn14-Conjugated Prussian Blue Nanoparticles as a Targeted Photothermal Therapy Agent for Glioblastoma

Authors

Nicole F. Bonan, George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.
Debbie K. Ledezma, George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.
Matthew A. Tovar, George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.
Preethi B. Balakrishnan, George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.
Rohan Fernandes, George Washington Cancer Center, George Washington University, Washington, DC 20052, USA.

Document Type

Journal Article

Publication Date

8-1-2022

Journal

Nanomaterials (Basel, Switzerland)

Volume

12

Issue

15

DOI

10.3390/nano12152645

Keywords

aFn14 antibody; glioblastoma; immunogenic cell death; photothermal therapy; prussian blue nanoparticles; targeted therapy; thermal therapy

Abstract

Prussian blue nanoparticles (PBNPs) are effective photothermal therapy (PTT) agents: they absorb near-infrared radiation and reemit it as heat via phonon-phonon relaxations that, in the presence of tumors, can induce thermal and immunogenic cell death. However, in the context of central nervous system (CNS) tumors, the off-target effects of PTT have the potential to result in injury to healthy CNS tissue. Motivated by this need for targeted PTT agents for CNS tumors, we present a PBNP formulation that targets fibroblast growth factor-inducible 14 (Fn14)-expressing glioblastoma cell lines. We conjugated an antibody targeting Fn14, a receptor abundantly expressed on many glioblastomas but near absent on healthy CNS tissue, to PBNPs (aFn14-PBNPs). We measured the attachment efficiency of aFn14 onto PBNPs, the size and stability of aFn14-PBNPs, and the ability of aFn14-PBNPs to induce thermal and immunogenic cell death and target and treat glioblastoma tumor cells in vitro. aFn14 remained stably conjugated to the PBNPs for at least 21 days. Further, PTT with aFn14-PBNPs induced thermal and immunogenic cell death in glioblastoma tumor cells. However, in a targeted treatment assay, PTT was only effective in killing glioblastoma tumor cells when using aFn14-PBNPs, not when using PBNPs alone. Our methodology is novel in its targeting moiety, tumor application, and combination with PTT. To the best of our knowledge, PBNPs have not been investigated as a targeted PTT agent in glioblastoma via conjugation to aFn14. Our results demonstrate a novel and effective method for delivering targeted PTT to aFn14-expressing tumor cells via aFn14 conjugation to PBNPs.

APA Citation

Bonan, Nicole F.; Ledezma, Debbie K.; Tovar, Matthew A.; Balakrishnan, Preethi B.; and Fernandes, Rohan, "Anti-Fn14-Conjugated Prussian Blue Nanoparticles as a Targeted Photothermal Therapy Agent for Glioblastoma" (2022). GW Authored Works. Paper 1560.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1560

Department

Medicine