IR808-ATIPA: A Dual-Function Agent for Enhanced Computed Tomography Imaging and Radiotherapy Sensitization in Cervical Cancer Treatment.

Abstract

Radiotherapy is pivotal in localized cancer treatment, yet balancing therapeutic efficacy with collateral tissue damage remains challenging. Conventional iodinated contrast agents, limited by rapid metabolism and short imaging windows, hinder precise radiotherapy planning. We developed IR808-ATIPA, a tumor microenvironment-responsive iodine-based compound integrating computed tomography (CT) imaging and radiosensitization. Synthesized by covalently linking IR808 and ATIPA, IR808-ATIPA leverages iodine's x-ray attenuation for high-contrast imaging while enhancing radiation dose deposition in cervical cancer. Unlike conventional agents, its prolonged tumor retention improves imaging accuracy and therapeutic targeting. Evaluations in HeLa tumor-bearing nude mice demonstrated superior in vitro/in vivo imaging performance and sustained tumor accumulation. RNA sequencing revealed that IR808-ATIPA enhances radiotherapy efficacy by activating the ferroptosis pathway via increased reactive oxygen species production and amplified x-ray absorption. Safety assessments confirmed no notable toxicity to major organs. IR808-ATIPA functions dually as a CT contrast agent for precise tumor delineation and a radiosensitizer promoting ferroptosis-mediated radiotherapy enhancement. Its extended intratumoral retention enables targeted therapy, minimizing off-target effects. These findings highlight IR808-ATIPA as a promising theranostic agent, bridging imaging-guided precision and therapeutic efficacy to advance personalized cancer treatment.