Fibrosis Disruption: SMITE Protocol for RT-Activated Anti-Fibrotic Nanoparticle
Pulmonary Fibrosis (PF) is a deadly progressive lung disease with no cure and very few effective treatments. Our dual-innovation therapy $-$ SMITE radiotherapy protocol and a radiation-activated anti-fibrotic nanoparticles - targeting fibrosis at its core: the pathological extracellular matrix (ECM). SMITE protocol delivers low dose, high-dose rate, spatially fractionated radiation to selectively disrupt fibrotic tissue, while priming the lung for localized drug release. Inhaled nanoparticles respond to radiation-triggered Reactive Oxygen Species (ROS) burst to release taladegib, a Hedgehog pathway inhibitor, directly involved into scarred tissue. This precision approach transforms fibrosis from a managed condition to a treatable target. With scalable preclinical development and a US-focused commerical trajectory, our proposed innovation offers a paradigm shift for pulmonary fibrosis care.