Diradicaloid-Loaded\nPolypeptide Nanoparticles for\nTwo-Photon NIR Phototheranostics

Stable organic radicals, with unique electronic transitions\nfrom\nthe ground state (D<sub>0</sub>) to the doublet excited state (D<sub>1</sub>), show promise as high-fluorescence quantum yield dyes. While\norganic small-molecule photosensitizers (PSs) have advanced for tumor\nphotodynamic therapy (PDT), opportunities exist to enhance their performance\nand functionality. Herein, we synthesized Thiele’s fluorocarbon\nderivative diradicaloid TFC-I with nearly 100% PLQY and integrated\nit into amphiphilic polypeptide nanoparticles, P-TI, using a precursor-doping\napproach. P-TI demonstrated notable features including high photostability,\naggregation-induced emission, bright near-infrared fluorescence, substantial\nquantum yield (37% PLQY), robust near-infrared two-photon absorption\n(∼400 GM cross section), and superior ROS generation compared\nto commercial PSs. <i>In vitro</i> and <i>in vivo</i> experiments confirmed that P-TI performed well in mitochondria-targeted\nPDT, two-photon fluorescence imaging, and biosafety. This work highlights\nthe use of organic stable radicals with precursor-doping for efficient\nPDT and deep tumor tissue imaging.