Work

A Radioresistant‐Tumor‐Targeted Nanoparticle for X‐Ray‐Controlled Nitric Oxide Release to Potentiate Radiotherapy

Year: 2026

Type: article

Abstract: Nitric oxide (NO) treated radioresistant tumors by relieving hypoxia and blocking DNA repair, but its nonselective toxicity has precluded therapeutic use. Here, we introduce a radioresistant tumor-selective NO nanogenerator that releases NO exclusively within the irradiated field. We identified BNN6 as a uniquely radiosensitive NO donor and loaded it into Glucose-Regulated Protein 78 (GRP78)-targeted nanocarrier to obtain PBTN, exploiting the overexpression of GRP78 in radioresistant cancers for selective accumulation. Upon irradiation, BNN6 undergoes one-electron reduction to release NO exclusively within the irradiated volume. NO combines radiation-induced reactive oxygen species to form peroxynitrite, provoking tumor DNA breaks while simultaneously suppressing DNA repair. In CT26 tumor-bearing mice, the combination of radiotherapy with PBTN and anti-PDL1 antibody achieved a tumor growth suppression of 96.5% and 80% survival at 40 days post-treatment. This tumor-targeted, irradiation-triggered NO nanogenerator thus offers a safe, precise, and translatable strategy to overcome radioresistance.

Source: Advanced Science

DOI: 10.1002/advs.202518233