Phototheranostic nanoparticles with aggregation-induced emission as a four-modal imaging platform for image-guided photothermal therapy and ferroptosis of tumor cells.

Due to the aggregation-caused quenching (ACQ) and weak photo-penetrating ability, the application of phototheranostic agents in drug delivery field is greatly limited. Ferroptosis, a newly discovered cell death mode, has not been extensively studied in the field of phototherapy up to now. Here, a new near-infrared II (NIR-II) molecule with aggregation-induced emission (AIE) property (named TSST) co-assembled with DHA-PEG and ferrocene as nanoparticles (DFT-NP), which was rationally designed and synthesized. The DFT-NP exhibited enhanced NIR-II fluorescence, photothermal, photoacoustic, magnetic resonance imaging, AIE and ferroptosis capacities. The NIR-II fluorescence intensity of obtained nanoparticles was improved, owing to the strong interaction between DHA and TSST, which limited the intramolecular rotation restriction and non-radiative attenuation of TSST to discourage energy dissipation in aggregation state. Inspiringly, the generated photothermal effect by DFT-NP can promote the Fenton reaction of ferrocene and HO, resulting in dissolution of the nanoparticles and cancer cells expedited ferroptosis via accumulation lipid free radicals of DHA. The released TSST enhanced the photothermal and photoacoustic imaging effects through removing the DHA restriction to restore the non-radiative attenuation. This work is the first example of nanoparticles that integrates four-mode imaging, photothermal and ferroptosis-induced therapy functions, which offers great advantages for potential clinical applications.