NIR-II aza-BODIPY photosensitizers with enhanced ICT effect for photothermal therapy of breast cancer

Enhancing intramolecular charge transfer (ICT) is a well-established approach to achieving red-shifted absorption and emission in aza-BODIPY derivatives. However, highly planar π-conjugated structures, commonly employed to strengthen ICT, often induce strong intermolecular π–π stacking, leading to reduced quantum yields, and consequently diminishing the overall photophysical performance. We introduced moderately electron-donating, non-planar 1-ethyl-1,2,3,4-tetrahydroquinoline units at the 1,7-positions and further enhanced donor strength at the 3,5-positions of the aza-BODIPY core to synthesized a series of aza-BODIPY photosensitizers: NJ1088, NJ1100, and NJ1150. NJ1150 displayed a pronounced absorption peak at 967 nm and retained substantial absorption beyond 1100 nm. Density Functional Theory (DFT) calculations confirmed that NJ1150 has a reduced HOMO–LUMO gap of 1.45 eV, consistent with its long-wavelength absorption. Moreover, the observed increase in Stokes shifts correlated with stronger donor groups further corroborates the intensified ICT effect in the series. Fluorescence studies revealed that NJ1150 exhibited a relatively high quantum yield of 1.89 % in DCM. Photothermal conversion studies demonstrated that NJ1150 encapsulated in PLX nanoparticles (NJ1150@PLX) reached 64 % conversion efficiency under 1064 nm laser irradiation. In vitro assays confirmed that 1064 nm laser irradiation of NJ1150@PLX induced significant tumor-cell apoptosis. Finally, evaluation in an orthotopic breast cancer mouse model revealed that NJ1150@PLX provided excellent second near-infrared window (NIR-II) fluorescence imaging and effectively suppressed tumor growth via photothermal therapy.