Harnessing Synergistic Interplay of Twisted and Planar Structures for the Development of NIR-II Phototheranostic Agents

Developing phototheranostic agents capable of simultaneous cancer diagnosis and therapy, particularly those emitting in the second near-infrared region (NIR-II, 1000-1700 nm), offers considerable prospects. However, achieving efficient fluorescence imaging (FLI) and heat generation for photothermal therapy (PTT) by NIR-II organic dyes remains a challenge primarily due to inadequate photon absorption and competitive energy dissipation pathways. Herein, we employed a molecular design strategy termed "planar core + twisted periphery" to develop a NIR-II phototheranostic agent, 4TPE-TB. This molecule features a coplanar central core to enhance intramolecular conjugation and four highly twisted peripheral rotors to suppress detrimental intermolecular stacking. 4TPE-TB exhibits high molar absorptivity (4.0 × 10⁴ M^-1 cm^-1), excitation at long wavelengths (980 nm), and desirable fluorescence and photothermal performance, superior to its analogs synthesized using previous molecular strategies. By formulating 4TPE-TB into nanoparticles, we successfully achieved high-precision NIR-II FLI and efficient PTT in cancer models. And we find out the dual role of the nanoparticles in direct tumor ablation and immune system activation, reinforcing their potential as a powerful therapeutic platform for cancer treatment. This work highlights a successful design rationale of NIR-II phototheranostic agents, offering the potential to enhance the precision and efficacy of cancer diagnostics and treatments.