Near-infrared (NIR)
dyes are widely used in the field of in vivo phototheranostics.
Hemicyanine dyes (HDs) have recently received tremendous attention due to their easy synthesis and excellent NIR features. However, HDs can easily form non-fluorescent aggregates and their potential for
phototherapy still needs further exploration due to their poor ability to generate
reactive oxygen species (ROS). Herein, a series of
hemicyanine dyes with different chalcogen atom (O, S, Se) substitutions were constructed to achieve optimized potential for phototheranostics. By replacing O with the heavy atom Se in the
xanthene skeleton, CySe-NEt2 showed much more favourable features such as extended NIR absorption/emission wavelength, boosted 1O2 generation rate and higher photothermal effect. In addition, a poly(
ethylene glycol) (PEG) group was introduced into the scaffold and yielded a nanotheranostic agent CySe-mPEG5K, which easily formed nanoparticles with appealing features such as excellent photostability, effective prevention of unpleasant H-aggregation, fast/selective
tumor accumulation and minimum dark toxicity. Solid
tumor growth was significantly suppressed through combined
photodynamic therapy (
PDT) and
photothermal therapy (PTT) guided by NIR fluorescence (NIRF) and photoacoustic (PA) imaging. This study not only presents the first example of
selenium-substituted
hemicyanine dyes, but also offers a reliable design strategy for the development of potent NIR phototheranostic agents with multi-mode imaging-guided combination therapeutic ability.