Cationic Nano Single Crystals: From In Situ Structural Determination to Synergistic Photoimmunotherapy

Organic single crystals with high charge-carrier mobilities and low trap densities exhibit more advantages than their corresponding amorphous or polycrystal materials in charge separation and transfer. This is also beneficial to type-I reactive oxygen species generation in achieving effective photoimmunotherapy. However, their design and preparation in nanoscale is still challenging. Herein, after the analysis of these reported organic photosensitizers (PSs), a principle in enhancing the proportion of hydrogen bonds but keeping their proper dipole moments in PSs was proposed to prepare the corresponding nano single-crystals (NSCs). Then, a D-A⁺-D-typed DTZP-PF₆^- is designed, and its NSCs (DTZP-PF₆^- NSCs) in high quality are successfully prepared by a seed-mediated strategy. After being characterized by three-dimensional electron diffractions (3D-ED), an H-type molecular arrangement with a slip angle of 66.93° is observed in DTZP-PF₆^- NSCs. This is much different from the packing modes in the common micrometer-sized DTZP-PF₆^- crystals cultured by solvent evaporation. Furthermore, benefiting from their defect-free crystal structures and efficient charge separation, DTZP-PF₆^- NSCs exhibit the specialties in type-I ROS generation; however, type-II ROS mainly occur in their corresponding amorphous nanoparticles. This then effectively induces pyroptosis and immunogenic cell death by mitochondrial oxidative stress under both normoxic and hypoxic conditions, promoting the ROS-induced photoimmunotherapy. Finally, the tumor growth can be well inhibited by DTZP-PF₆^- NSCs for the successfully activation of antitumor immunity. Our research here provides an effective principle for designing, preparing, and characterizing the organic NSCs, as well as a better understanding the structures and packing of organic nanomaterials in situ, which is much significant to study their performance in aggregates.