RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy.

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for the treatment of cancer. Existing photosensitizers are predominantly engineered to target diverse biomolecules, including proteins, DNA, lipids, and carbohydrates, and have proven to greatly enhance the efficacy or specificity of PDT. However, it is noteworthy that there exists a conspicuous scarcity of photosensitizers specifically designed to target RNAs. Recognizing the crucial and multifaceted roles played by RNAs in various cellular processes and disease states, we have ventured into the development of a novel RNA-targeting photosensitizer, named Se-718, designed specifically for PDT-based cancer therapy. Se-718 has been engineered to exhibit a high molar absorption coefficient in the NIR region, which is crucial for effective PDT. More importantly, Se-718 has demonstrated a distinct RNA-targeting capability, as evidenced through rigorous testing in both circular dichroism and fluorescence experiments. Furthermore, Se-718 has been shown to display both type I and type II photodynamic properties. This unique characteristic enables the efficient killing of cancer cells under a wide range of oxygen conditions, both normoxic (21% O2) and hypoxic (2% O2). The IC50 of Se-718 can be as low as 100 nM, and its light-to-dark toxicity ratio is an impressive 215 times higher, outperforming most photosensitizers currently available. Moreover, in vivo studies conducted with tumor-bearing mice have demonstrated the excellent antitumor effects and high safety profile of Se-718. Considering the outstanding PDT efficacy of Se-718, we are optimistic that the development of RNA-targeting photosensitizers may provide an innovative and highly effective option for cancer therapeutics in the near future.

Water-soluble fluorescent probes for differentiating cancer cells and normal cells by tracking lysosomal viscosity.

Lysosomal viscosity is a significant parameter of lysosomes and closely related to various diseases. Herein, two fluorescent probes, Lyso-vis-A and Lyso-vis-B, were developed, which demonstrate diverse advantages, including great water solubility, lysosome targeting ability and viscosity sensitivity. In particular, Lyso-vis-A exclusively showed fluorescence response toward viscosity but was not influenced by pH changes, rendering it a selective lysosomal viscosity probe. Furthermore, Lyso-vis-A was successfully applied to monitor lysosomal viscosity variations in living cells and differentiate cancer cells and normal cells.

Reaction-based fluorescent and chemiluminescent probes for formaldehyde detection and imaging.

Formaldehyde (FA), a reactive carbonyl species, is classified as Group 1 carcinogen by International Agency for Research on Cancer (IARC) in 2004. In addition, clinical studies have implicated that elevated levels of FA have been associated with different kinds of diseases, such as neurodegenerative diseases, diabetes, and chronic liver and heart disorders. However, in addition to the direct inhalation of FA in the environment, most organisms can also produce FA endogenously by demethylases and oxidases during the metabolism of amino acids and xenobiotics. Since FA plays an important role in physiological and pathological processes, developing reliable and efficient methods to monitor FA levels in biological samples is crucial. Reaction-based fluorescent/chemiluminescent probes have provided robust methods for FA detection and real-time visualization in living organisms. In this highlight, we will summarize the major developments in the structure design and applications of FA probes in recent years. Three main strategies for designing FA probes have been discussed and grouped by different reaction mechanisms. In addition, some miscellaneous reaction mechanisms have also been discussed. We also highlight novel applications of these probes in biological systems, which offer powerful tools to discover the diverse functions of FA in physiology and pathology processes.