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Abstract Polymeric donors of gasotransmitters, gaseous signaling molecules such as hydrogen sulfide, nitric oxide, and carbon monoxide, hold potential for localized and extended delivery of these reactive gases. Examples of gasotransmitter donors based on polysaccharides are limited despite the availability and generally low toxicity of this broad class of polymers. In this work, we sought to create a polysaccharide H2S donor by covalently attachingN‐thiocarboxyanhydrides (NTAs) to amylopectin, the major component of starch. To accomplish this, we added an allyl group to an NTA, which can spontaneously hydrolyze to release carbonyl sulfide and ultimately H2S via the ubiquitous enzyme carbonic anhydrase, and then coupled it to thiol‐functionalized amylopectin of three different molecular weights (MWs) through thiol‐ene “click” photochemistry. We also varied the degree of substitution (DS) of the NTA along the amylopectin backbone. H2S release studies on the six samples, termed amyl‐NTAs, with variable MWs (three) and DS values (two), revealed that lower MW and higher DS led to faster release. Finally, dynamic light scattering experiments suggested that aggregation increased with MW, which may also have affected H2S release rates. Collectively, these studies present a new synthetic method to produce polysaccharide H2S donors for applications in the biomedical field.
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Recent advance in self‐assembled polymeric nanomedicines for gaseous signaling molecule delivery
Abstract Gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) 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
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- Award ID(s):
- 2102848
- PAR ID:
- 10471937
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- WIREs Nanomedicine and Nanobiotechnology
- Volume:
- 16
- Issue:
- 1
- ISSN:
- 1939-5116
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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