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Life sciences · Journal article
Analytical Chemistry · September 25, 2026
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Abstract Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), offers a minimally invasive approach with precise spatiotemporal control for cancer treatment. However, conventional photosensitizers are prone to aggregation-caused quenching, which lowers quantum yields, while their short wavelengths limit tissue penetration. Aggregation-induced emission luminogens (AIEgens) provide an effective solution. Although rotor engineering has enabled the development of AIEgens with improved quantum yields and red-shifted emission, current studies still focus mainly on single-rotor systems. In particular, triphenylamine (TPA) and tetraphenylethylene (TPE), two widely used rotor motifs in AIE systems, have rarely been systematically compared to clarify their distinct photophysical roles or cooperatively integrated for optical regulation. Here, two donor–acceptor AIEgens, TPAFA and TPEFA, were designed to elucidate the photophysical impact of cross-rotor coassembly. TPAFA exhibits intense NIR-II fluorescence but displays limited photothermal effects, whereas TPEFA shows enhanced NIR-II absorption and photothermal efficiency, albeit with diminished emission. Leveraging their complementary strengths, cross-rotor coassembly of TPAFA and TPEFA with disulfide-linked PEG generated glutathione-responsive nanoparticles. This strategy preserved the bright emission of the TPAFA component and the long-wavelength photothermal activity of the TPEFA component, enabling NIR-II fluorescence imaging and 808/1064 nm dual-band PTT with improved deep-tissue applicability. With 97.29% tumor inhibition in vivo and good biocompatibility, this study demonstrates that cross-rotor integration is an effective strategy for functionally integrating complementary fluorescence-emission and therapy-related energy-dissipation properties, thereby enabling the rational design of AIEgens for NIR-II-associated phototheranostic applications.