Synchrotron Microbeam Radiation Therapy in Combination With Gold Nanoparticles Improves Control of Mouse Melanoma
Cristian Fernandez-Palomo1, Marine Potez2, David Haberthür1
1Institute of Anatomy, University of Bern, Bern, Switzerland.
Purpose:
Microbeam radiation therapy (MRT) is a preclinical, spatially fractionated radiation therapy technique that delivers ultranarrow synchrotron x-ray beams at ultrahigh dose rates. MRT has demonstrated superior tumor control compared with synchrotron broad beam by triggering infiltration of CD8+ T cells and inducing a transient vascular permeability window. This study aimed to investigate the effects of combining MRT with gold nanoparticles (AuNPs) on tumor growth, while also assessing whether MRT could enhance intratumoral accumulation of AuNPs.
Methods And Materials:
Mice bearing B16-F10 melanoma in their ears were assigned to 7 experimental groups, each receiving distinct combinations of priming MRT (150 Gy peak dose), AuNPs, broad beam (6.1 Gy), and therapeutic MRT (400 Gy peak dose). MRT was delivered as an array of 50-µm-wide beams spaced 200 µm apart. Tumor growth was monitored daily, whereas 15-nm AuNP uptake was assessed with microCT imaging, electron microscopy, and Image Mass Cytometry.
Results:
Priming MRT increased intratumoral AuNP accumulation by 2.5-fold on day 3 and 2.3-fold on day 5 compared with nonprimed controls. Image Mass Cytometry showed that AuNPs distributed across the tumor stroma and concentrated at the tumor periphery, near areas with high vascular density and in M2-like macrophages. Combining priming MRT with AuNPs and therapeutic MRT achieved the best tumor growth delay and regression with a median survival to 39.5 days; significantly longer than the 17 days achieved with priming MRT, AuNPs, and broad beam. The sensitizer enhancement ratio of 1.38 highlighted the efficacy of AuNP-enhanced MRT.
Conclusions:
Our study introduces a novel approach in cancer therapy, demonstrating that MRT serves as both a potent standalone treatment and an effective enhancer of drug delivery. MRT increased the tumoral concentration of AuNPs and could potentially do the same with other therapeutic agents. Our findings strongly advocate for the continued development of MRT-based combination regimens and highlight the clinical potential of this dual-mechanism approach.
