Polymeric Nanomedicines for Controlled Release of Sulfur Dioxide

Sulfur dioxide (SO2), previously regarded as one of industrial waste gas, has recently been identified as a novel gasotransmitter in living things. SO2 could be endogenously produced from the metabolism of sulfur-containing amino acids. The endogenous SO2 can regulate many biological processes, physiological and pathophysiological events. However, excessive cellular SO2 would cause serious oxidative damages to DNA, proteins, and lipids, and affect the apoptosis-related gene expression in cells. This can be explained by the ability of SO2 to deplete GSH and induce generation of ROS in cell. Thus, SO2 has great potential in cancer treatment. However, the traditional inhalation of SO2 is not suitable for clinical use because of its unpleasant odor. Similarly, using mixed sulfites as donors of SO2 also cannot meet clinical needs due to their rapid excretion from body. To address these issues, a series of stimuli-responsive SO2-releasing small-molecule donors have been developed for controlled release of SO2. Most of these small-molecule SO2 donors exhibit controlled release behaviors and show great potency for therapeutic application. However, the poor water solubility and lack of tumor-targeting ability significantly hamper the clinical translation of these small-molecule SO2 donors. Very recently, polymeric nanomedicines with controlled SO2-releasing ability have been developed through directly conjugating SO2-releasing donors onto the side chains of polymer or loading the SO2-releasing donors inside the polymeric nanocarriers. The resultant polymeric nanomedicines can achieve improved accumulation and targeted release of SO2 in tumor sites, leading to enhanced anti-cancer efficacy and ameliorated side effect. All in all, our review firstly summarizes the chemical structure and release mechanisms of small-molecule SO2 donors, and subsequently, the research progress of SO2-releasing polymeric nanomedicines is highlighted. Finally, the challenges and future perspectives on the development of SO2-releasing polymeric nanomedicines are briefly discussed. [GRAPHICS] .