A dual-type I/II NIR photosensitizer for effective cancer photodynamic therapy with enhanced ROS generation

Based on the cyanine dye scaffold, two photosensitizers (PSs) (C1 and C2) were successfully synthesized. These PSs exhibited a maximum absorption wavelength of 660 nm, falling within the near-infrared window. Compared to the commercially available photosensitizer ICG, the newly developed PSs demonstrated enhanced reactive oxygen species (ROS) generation under lower light doses. Notably, these PSs can simultaneously produce both singlet oxygen (¹O₂) and superoxide anion radicals (O₂˙^-), classifying them as dual type I/II PSs. Compared with C1, the ¹O₂ quantum yield of C2 was higher, as high as 10.6 times that of ICG. Theoretical calculations revealed that the molecules of C2 possessed a small singlet-triplet energy gap (ΔE _S-T), which facilitated more efficient intersystem crossing (ISC) from the singlet to triplet state, thereby promoting greater ROS generation. Experiments showed that C1 and C2 were located in mitochondria and could cause a decrease in mitochondrial membrane potential, leading to cell death. Animal experiments have shown that C2 effectively suppressed tumor growth without side effects.