Tongue cancer tailored photosensitizers for NIR-II fluorescence imaging guided precise treatment

Although several photosensitizers have been used for photodynamic therapy (PDT) of tongue cancer, the treatment efficacy was still suffered from the short excitation wavelength of photosensitizer, low reactive oxygen species (ROS) yield in hypoxic tumor microenvironment and lack of monitoring method. Herein, by introducing two electron - deficient groups (A) on D-A′-D core, a novel near-infrared II (NIR-II) molecule with A-D-A′-D-A configuration is developed. Via the rational design of molecular structure, NIR-II molecule exhibits excellent properties: i) The intramolecular multiple “push-pull” interactions and the enlargement of conjugated system results in the absorption wavelength red-shift, so that the photosensitizers could be effectively excited by NIR laser (808 nm). ii) The reduced ΔEST promotes the intersystem crossing (ISC) process and enables high-efficient generation of ·OH via Type I PDT, addressing the limitation of hypoxic tumor. iii) The high emission of NIR-II fluorescence and excellent optical stability endow the repeated NIR-II imaging to report the precise localization of tongue tumor for guiding laser irradiation and monitoring treatment, so as to achieve precise dose and timing of administration and minimize the side effect. Therefore, this work will provide insights into design of tongue cancer tailored photosensitizers for precise and effective therapy. [Display omitted] •Herein, by introducing two “A” onto both ends of D-A′-D core to prepare a larger conjugation system (named NIR-II molecule).•Owing to the enlargement of conjugated system, the absorption and fluorescence were significantly red-shifted.•Due to the reduced ∆Est, the PDT-related intersystem crossing process was enhanced, leading to stronger PDT performance.•NIR-II-H could generate ·OH via Type-I PDT process, which is beneficial to overcome the hypoxia-resistance photodynamic effect.•Through NIR-II fluorescence imaging, orthotopic tongue cancer and surrounding normal tissue can be well differentiated.•NIR-II-H NPs could selectively target into orthotopic tongue tumor and exerted a potent outcome via synergistic PDT and PTT.