ABSTRACT The efficient delivery of theranostic nanoprobes to tumor sites remains a major challenge, often hindering precise tumor imaging and effective treatment. In this study, we present a novel strategy for the in situ generation of imaging and radiosensitizing nanoprobes inside tumors, enabling responsive photoacoustic imaging and targeted radiotherapy. The designed organic–inorganic hybrid nanoprobe is composed of a copper‐based layered double hydroxide (Cu‐LDH) intercalated with the near‐infrared organic dye IR‐806, serving as a photoacoustic imaging agent (designated as CAL‐IR). Upon exposure to hydrogen sulfide (H 2 S) in colorectal tumor microenvironments, the nanoprobe undergoes activation and transforms in situ into copper sulfide (Cu 2 − x S) nanoparticles. The newly formed Cu 2 − x S/LDH heterojunction nanostructure exhibits significantly enhanced near‐infrared absorption, while concurrently promoting radiotherapy efficacy through multiple mechanisms: consumption of endogenous H 2 S, reduction of X‐ray attenuation, and intrinsic radiosensitization. This unique system allows high‐contrast photoacoustic imaging and, consequently, achieves improved radiotherapy outcomes in mouse models of colorectal cancer, with minimal off‐target effects. These results underscore the promising clinical potential of CAL‐IR for precision tumor imaging and enhanced radiotherapy.
Zhu et al. (Sun,) studied this question.
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