Fn14-Targeted Gold Nanorods for Augmenting Laser Thermal Therapy for High-Grade Gliomas

Glioblastoma (GBM) is a highly aggressive and invasive brain tumor. Tumor recurrence after standard surgery, chemotherapy, and radiation is nearly universal. Unfortunately, only around 25% of GBM patients undergo repeat surgery. Laser interstitial thermal therapy (LITT) is a promising strategy to treat patients with inoperable or recurrent GBM. While advances in magnetic resonance thermometry and laser probe cooling systems have provided significant safety improvements, the full potential of laser thermal therapy is still hindered by the lack of selective targeting of GBM cells. Gold nanorods (GNR) are attractive plasmonic antennas that can efficiently convert laser energy to localized heat for hyperthermal therapy and can be used as contrast agents for computed tomography (CT) imaging. Here, we surface-functionalized GNR with antifibroblast growth factor-inducible 14 (Fn14) antibody and polyethylene glycol to achieve GBM selectivity with low adhesivity to extracellular matrix. Red light activation (690 nm, 2.5 W/cm²) of our decreased adhesivity, receptor-targeted gold nanorods (DART-GNRs) raised the temperature of brain tissue-mimicking agarose phantoms by 20 °C within 1 min. DART-GNRs selectively targeted Fn14-positive GBM cells and, upon light activation, enhanced photothermal killing by 5.2-fold, compared to nontargeted GNRs. Finally, DART-GNR can provide contrast for CT imaging in phantoms, which can be further investigated for image-guided laser thermal therapy in vivo and eventually for GBM patients undergoing LITT.