Abstract
The rational design of organic phototheranostic agents that combine diagnostic and therapeutic capabilities for cancer treatment remains challenging due to the inherent competition between radiative and non-radiative energy dissipation pathways. Herein, a novel molecule, TQP-TTPA, is strategically designed by incorporating a bulky electron donor and extended π-bridge, resulting in red-shifted absorption and emission in the second near-infrared window (NIR-II), along with prominent NIR-IIa emission (1300-1500 nm), a high NIR-II extinction coefficient, and enhanced NIR-IIa fluorescence brightness and photothermal conversion efficiency (43.8 %). These favorable properties are attributed to the strong donor-acceptor (D-A) interaction and enhanced intramolecular motion. Quantum chemical calculations provide insights into the excited-state energy dissipation mechanism and the role of intramolecular motion in modulating photophysical behavior. Furthermore, the femtosecond transient absorption (fs-TA) spectroscopy reveals that the performance enhancement originates from efficient intramolecular charge transfer (ICT) and promoted intramolecular motion by rational donor/π-bridge engineering. Based on these advantages, alendronate-functionalized TQP-TTPA nanoparticles (TQP-TTPA@ALD NPs) are developed for precise and high-resolution NIR-II fluorescence (FLI), photoacoustic (PAI), and phototherml (PTI) trimodal imaging-guided high-efficiency photothermal therapy (PTT) of prostate cancer bone metastases. This work offers a molecular-level design strategy for organic phototheranostics with tunable radiative/non-radiative decay balance, bridging fundamental photophysics and precision cancer theranostics.