Host-Guest supramolecular Cubes: A versatile engineering system of squaraine and Cuburbit[8]uril for selective fluorescence imaging and enhanced photodynamic therapy in tumor cells

The development of a multifunctional system capable of selectively performing fluorescence imaging within tumors and exhibiting enhanced anti-tumor efficacy represents a significant advancement in fluorescence imaging-guided tumor treatment. Near-infrared (NIR) fluorescent photosensitizers have emerged as promising tools for tumor diagnosis and therapy due to their ability to minimize background interference and penetrate deeper tissues. However, there remain limitations that impede their practical application. Herein, we propose a supramolecular photosensitizer system, SQ-DPA⊃CB[8], achieved through host–guest interactions between the NIR squaraine dye SQ-DPA and cuburbit[8]uril (CB[8]) for tumor imaging and photodynamic therapy (PDT). Leveraging the excellent recognition and encapsulation properties of CB[8], the photosensitizer system self-assembles into uniform cubes. Compared to the precursor SQ-DPA, the assembled SQ-DPA⊃CB[8] supramolecular complexes selectively enhancing accumulation in the mitochondria of tumor cells, while substantially reduce dark toxicity. Furthermore, they effectively alleviate photobleaching of SQ-DPA, significantly extending the duration of phototherapy. In vitro and in vivo experiments emphasize the enhanced photodynamic therapy potential of SQ-DPA⊃CB[8] complexes. This work presents a novel approach for constructing high-performance imaging-guided photosensitizers through supramolecular self-assembly, addressing the limitations encountered in current applications.