Recent advance in self-assembled polymeric nanomedicines for gaseous signaling molecule delivery.

Gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S) have recently been recognized as essential signal mediators that regulate diverse physiological and pathological processes in the human body. With the evolution of gaseous signaling molecule biology, their therapeutic applications have attracted growing attention. One of the challenges in translational research of gaseous signaling molecules is the lack of efficient and safe delivery systems. To tackle this issue, researchers developed a library of gas donors, which are low molecular weight compounds that can release gaseous signaling molecules upon decomposition under physiological conditions. Despite the significant efforts to control gaseous signaling molecule release from gas donors, the therapeutic potential of gaseous signaling molecules cannot be fully explored due to their unfavorable pharmacokinetics and toxic side effects. Recently, the use of nanoparticle-based gas donors, especially self-assembled polymeric gas donors, have emerged as a promising approach. In this review, we describe the development of conventional small gas donors and the challenges in their therapeutic applications. We then illustrate the concepts and critical aspects for designing self-assembled polymeric gas donors and discuss the advantages of this approach in gasotransmistter delivery. We also highlight recent efforts to develop the delivery systems for those molecules based on self-assembled polymeric nanostructures. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Manganese Porphyrin-Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from a Hydrogen Sulfide Donor.

Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H2 S donor and manganese porphyrin-containing polymeric micelles (MnPMCs) that catalyze oxidization of H2 S to per/polysulfide species. MnPMCs serve as a catalyst for H2 S oxidation in aerobic phosphate buffer. HPLC-MS/MS analysis reveals that H2 S oxidation by MnPMCs in the presence of glutathione results in the formation of glutathione-SnH (n = 2 and 3). Furthermore, co-treatment of human umbilical vein endothelial cells with the H2 S donor anethole dithiolethione and MnPMCs increases intracellular per/polysulfide levels and induces a proangiogenic response. Co-delivery of MnPMCs and an H2 S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications.