A photoinduced nuclear translocation of thiophene derivative for selective chemotherapy

In this study, a novel thiophene-based small organic molecule, 2,5-bis(2-(N-butylpyridinium-4-yl)vinyl)-thiophene diiodine (BBT), was prepared. BBT not only presented selective dark/photo dual cell toxicity to cancer cells but also acted as a nuclear transport inducer for the chemotherapy agent doxorubicin (DXR), thereby promoting anticancer efficacy. BBT exhibits the special aggregation-induced emission (AIE) effect and specifically accumulates in the mitochondria of cancer cells, leading to higher dark toxicity in cancer cells than in normal cells. Interestingly, BBT molecules translocate into the nuclei of cancer cells upon photosensitisation and further selectively exert their phototoxicity on cancer cells. Thanks to the unique characteristics of BBT, a synergistic therapy was optimised based on several combinational treatment pathways between BBT and DXR. The effectiveness of the combinational treatment pathway was evaluated based on the theoretical and actual cell viability rates, the accumulation of DXR in cell nuclei, and the required time interval for the fragmentation of nucleoli. BBT pre-incubation, followed by photosensitisation and then DXR incubation, proved to be the most effective combinational treatment pathway, constituting the synergistic therapy. As a result, BBT is considered a nuclear translocation molecule that can be beneficial for nucleus-targetable chemotherapy drugs to promote nuclear aggregation and drug efficacy. Furthermore, because the nuclear translocation behaviour of BBT is selective in cancer cells, the nuclear aggregation enhancement of chemotherapy drugs can be achieved selectively. In conclusion, we developed a novel synergistic therapy for cancer treatment, and BBT is a potential chemotherapy auxiliary for DXR.