Nitric oxide release: part II. Therapeutic applications

Abstract

A wide range of nitric oxide (NO)-releasing materials has emerged as potential therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. In this tutorial review, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing.

Figure 1

Nitric oxide’s role in the vascular endothelium and its effects on cellular activities.

Figure 2

Implant-induced (A) thrombosis and injury-induced (B) thrombosis leading to restenosis.

Figure 3

The dual role of nitric oxide in cancer biology.

Figure 4

The numerous antibacterial mechanisms of nitric oxide and its byproducts (A) lead to decreased bacterial viability and decreased adhesion on NO-releasing surfaces (B) compared to control surfaces (C). Images of bacteria were obtained using atomic force microscopy.

Figure 5

Timeline of events that occur during the wound-healing cascade.