A molecular engineered NIR-II fluorescence agent with enhanced radiative and non-radiative decay for precision prostate cancer bone metastasis theranostics.

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.