Chitosan-based bimodal photosensitive system: Synergistic realization of visible light viscosity imaging and...

The integration of bioimaging and photodynamic therapy (PDT) joins real-time visualization with spatially controlled therapeutic activation, thus presenting a promising theranostic platform for precision oncology. However, the clinical translation of conventional photosensitizers suffers from limited tissue penetration and potential photodamage. To overcome these shortcomings, we proposed a NIR responsive system in this work. A naphthalimide-based small molecule (NQL) was synthesized, followed by oligo-chitosan conjugation through Schiff base formation, yielding the water-soluble probe CS-NQL. CS-NQL exhibits a twisted intramolecular charge transfer (TICT) state. It also has the capability to target lysosomes. This enables CS-NQL to respond to environmental viscosity, with target lysosomes. The CS-NQL was then electrostatically self-assembled with DNA to form nanoparticles (CS-NQL@DNA NPs). These nanoparticles (NPs) can generate reactive oxygen species (ROS) under 660 nm laser irradiation, exhibiting photosensitivity. Further detection using commercial reagents revealed this photosensitivity stems via Type I process. Critically, this oxygen-independent mechanism retained the ability to generate ROS under hypoxia, overcoming the limitations of the tumor microenvironment. Under 660 nm laser irradiation (0.4 W/cm²) for 20 min, NPs generate ROS, leading to apoptosis in over 90 % of HeLa cells and demonstrating antitumor effects. In vivo experiments, it is demonstrated that the NPs exhibited PDT after 30 min of 660 nm laser irradiation, achieving significant tumor suppression.