Self-immolative fluorinated nanotheranostics amplifying 19F MRI signals for tumor-specific imaging and photodynamic therapy

Fluorine-19 magnetic resonance imaging ( 19 F MRI) offers distinct advantages, including background-free signal detection, quantitative analysis, and deep tissue penetration. However, its application is currently limited by challenges associated with existing 19 F MRI contrast agents, such as short transverse relaxation times (T 2 ), limited imaging sensitivity, and suboptimal biocompatibility. To overcome these limitations, a glutathione (GSH)-responsive triblock copolymer (PB7), featuring self-immolative characteristics, has been developed. In aqueous solution, PB7 can spontaneously self-assemble into a 19 F MRI contrast agent (SPTF), which exhibits a long T 2 relaxation time and GSH-responsive T 2 prolongation. Notably, during the self-assembly process of PB7, the photosensitizer Chlorin e6 (Ce6) can be encapsulated inside of the hydrophobic domain of SPTF, resulting in the formation of a multifunctional nanotheranostic agent (Ce6@SPTF). Ce6@SPTF is able to undergo structural disintegration in response to elevated GSH levels at the tumor site, leading to the dissociation of fluorinated segments and a marked amplification of the 19 F MRI signal. Concurrently, the controlled release of Ce6 generates high levels of reactive oxygen species (ROS) under laser irradiation, enabling effective in vivo ablation of breast tumors. This study presents a promising strategy to effectively combine 19 F MRI with therapeutic interventions.