RNA-Activatable Near-Infrared\nPhotosensitizer for\nCancer Therapy

Photodynamic\ntherapy (PDT) has recently come to the forefront\nas\nan exceptionally powerful and promising method for the treatment of\ncancer. Existing photosensitizers are predominantly engineered to\ntarget diverse biomolecules, including proteins, DNA, lipids, and\ncarbohydrates, and have proven to greatly enhance the efficacy or\nspecificity of PDT. However, it is noteworthy that there exists a\nconspicuous scarcity of photosensitizers specifically designed to\ntarget RNAs. Recognizing the crucial and multifaceted roles played\nby RNAs in various cellular processes and disease states, we have\nventured into the development of a novel RNA-targeting photosensitizer,\nnamed <b>Se-718</b>, designed specifically for PDT-based cancer\ntherapy. <b>Se-718</b> has been engineered to exhibit a high\nmolar absorption coefficient in the NIR region, which is crucial for\neffective PDT. More importantly, <b>Se-718</b> has demonstrated\na distinct RNA-targeting capability, as evidenced through rigorous\ntesting in both circular dichroism and fluorescence experiments. Furthermore, <b>Se-718</b> has been shown to display both type I and type II photodynamic\nproperties. This unique characteristic enables the efficient killing\nof cancer cells under a wide range of oxygen conditions, both normoxic\n(21% O<sub>2</sub>) and hypoxic (2% O<sub>2</sub>). The IC<sub>50</sub> of <b>Se-718</b> can be as low as 100 nM, and its light-to-dark\ntoxicity ratio is an impressive 215 times higher, outperforming most\nphotosensitizers currently available. Moreover, in vivo studies conducted\nwith tumor-bearing mice have demonstrated the excellent antitumor\neffects and high safety profile of <b>Se-718</b>. Considering\nthe outstanding PDT efficacy of <b>Se-718</b>, we are optimistic\nthat the development of RNA-targeting photosensitizers may provide\nan innovative and highly effective option for cancer therapeutics\nin the near future.