Nitric Oxide-Activatable NIR-II Organic Small Molecule for Fluorescence Imaging-Guided Synergistic Photodynamic and Photothermal Therapy

Precise cancer diagnosis and treatment are vital to reducing mortality. The development of activatable second near-infrared window (NIR-II) imaging-guided tumor phototherapy strategies with excellent tumor specificity and antitumor effects remains a major challenge. In this work, we design and synthesize a D-π-A-π-D organic small molecule CTBA that can be effectively activated by nitric oxide. CTBA possesses the absorption and emission in the visible region. Interestingly, after reacting with excess nitric oxide in the tumor microenvironment, the probe can be converted into CTBT with a new structure, which exhibits excellent NIR-II fluorescence, photodynamic and photothermal properties under 808 nm excitation. Notably, this activatable probe pioneers the convergence of three critical features: (1) NIR-II imaging capacity for deep-tissue visualization, (2) on-demand therapeutic activation, and (3) synergistic photodynamic-photothermal effects, marking the first report of such an integrated system. By virtue of its "turn-on" property, this probe significantly reduces the background noise of imaging and the damage to normal tissues during phototherapy. Then, CTBA-NPs are constructed by self-assembly between CTBA and PS1000-PEG2000, which can achieve highly accurate and efficient tumor diagnosis and treatment in vitro and in vivo. This work provides a promising strategy for designing activatable multifunctional NIR-II fluorescent probes for precise theranostics.