Biomarker‐induced gold aggregates enable activatable near‐infrared‐II photoacoustic image‐guided radiosensitization

Abstract

Current radiotherapy (RT) lacks the ability to accurately discriminate between tumor and healthy tissues, resulting in significant radiation‐induced damage for patients. Therefore, there is an urgent need for precise RT techniques that can optimize tumor control while minimizing adverse effects on surrounding healthy tissues. In this study, we developed a nanodrug (AuNR@Peptide) composed of furin‐responsive RVRR peptide‐conjugated AuNRs, which integrates an activatable probe and a radiosensitizer into a single system for accurate tumor localization, enabling image‐guided precision RT. Upon reaching the tumor site after intravenous administration, proteolytic cleavage of RVRR substrates on AuNR@Peptide by biomarker triggers aggregation of gold nanorods (AuNRs) into larger aggregates, leading to activation of near‐infrared (NIR)‐II photoacoustic (PA) signals to precisely localize the tumor and enhance tumor retention by preventing migration and backflow of AuNRs. This significantly amplifies radiosensitivity efficiency. The peak time point at which the NIR‐II PA signal was observed at the tumor site after injection serves as a reference for initiating RT, demonstrating substantial improvement in tumor RT through investigations related to radiosensitization mechanisms. The integration of imaging and therapy in this study offers a promising image‐guided therapeutic modality for tumors.