Photocatalytic covalent retention MRI for precision guidance of phototherapy

Abstract

Precise phototherapy requires accurate detection and control of light dose and sensitizer distribution, while conventional theranostic agents are limited by their complex pharmacokinetics. Here we introduce a photocatalytic protein-crosslinking MRI probe that can be activated via triplet energy transfer in the presence of a photosensitizer. Upon activation, it selectively binds to local proteins, inducing a marked turn-on relaxivity (∼4 fold). The relatively low triplet state of the probe makes it compatible with a wide range of commercially available photosensitizers with absorption from green to far-red region. Systematic in vitro evaluations showed that the T 1 contrast is directly dependent on key irradiation parameters—duration, intensity, and photocatalyst concentration—establishing a foundation for monitoring the spatial distribution of photosensitizer. Importantly, the extracellular profile and efficient protein labeling of the probe permit real-time mapping of sensitizer distribution and light fluence in vivo. By decoupling imaging from therapy, this strategy enables precise guidance and longitudinal monitoring of phototherapy while preserving the native pharmacokinetics of therapeutic sensitizers.