Se-sensitized NIR-II merocyanine photosensitizer for mitochondria-targeted Type I photodynamic therapy of breast cancer in mice.

Breast cancer is one of the most prevalent malignant tumors affecting women worldwide and poses a serious threat to women's health and survival. Accordingly, the development of effective technologies for breast cancer treatment has received considerable attention in biomedicine and materials chemistry. Here, push-pull electronic and heavy-atom effects were incorporated into photosensitizer design. Methoxytriphenylamine was used as an electron donor to strengthen electron-donating capability, whereas the benzothiazolium cation served as an electron acceptor. By replacing the S atom in the electron acceptor with a Se atom, four NIR-II merocyanine photosensitizers, namely S-672, S-732, Se-720, and Se-780, were synthesized. All four compounds were classified as Type I photosensitizers. The introduction of Se markedly enhanced •OH generation, and the overall ROS generation efficiency followed the order: Se-780 > Se-720 > S-732 > S-672. Cellular experiments showed that Se-720 and Se-780 exhibited low cytotoxicity under dark conditions and specifically targeted mitochondria. Upon light irradiation, Se-720 and Se-780 showed superior PDT efficacy by damaging mitochondria and triggering immune responses. Nanoparticles prepared by encapsulating Se-780 with Pluronic F127 enabled targeted NIR-II fluorescence imaging of breast tumors in mice and effectively inhibited tumor growth.