Molecular Engineering of NIR-II Excitable Phototheranostic for Mitochondria-Targeted Cancer Photoimmunotherapy

The
advancement of mitochondria-targeted near-infrared-II
(NIR-II)
excitable phototheranostics constitutes a promising strategy for improving
fluorescence-image-guided cancer phototherapy. However, developing
phototheranostic agents that simultaneously combine high-contrast
NIR-II fluorescence imaging with effective multimodal therapeutic
techniques remains a substantial challenge. Herein, we reported a
shielding-donor–acceptor–donor-shielding structured
NIR-II phototheranostic (FCD-T) by a molecular engineering strategy,
followed by self-assembly with glutathione-responsive copolymer to
form FCD-T nanoparticles. The introduction of functional bithiophene
endows FCD-T with significant electron-donating properties and reduces
intermolecular π-π stacking interactions. The robust π-conjugation
of fluorene with good rigidity would enhance the intramolecular charge
transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption
peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light
excitation, such nanoparticles could generate excellent photothermal
and photodynamic performances with good biocompatibility. Moreover,
the NIR-II mitochondria-targeted phototherapy further facilitated
mitochondrial apoptosis-related pathways, activating antitumor immunity
and inhibiting tumor growth with single irradiation at low doses.