Research Progress of Nitric Oxide Donor in Antitumor Application

Nitric oxide (NO), the first discovered endogenous gas molecule participating in signal transduction pathway, widely exists in the human body and is involved in various physiological processes. The research on the relevant mechanisms of NO as a gas signaling molecule has confirmed its important physiological role in promoting vasodilation, preventing infection, stimulating soft tissue regeneration, and preventing platelet adhesion. In tumor cells, the cancer-inhibiting or cancer-promoting effect of NO is determined by its concentration, and the antitumor activity of NO has a high concentration dependence. High concentration of NO can react with intracellular superoxide anions and generate reactive nitrogen species such as peroxynitrite ions to induce apoptosis by damaging the DNA of cancer cells, inhibiting various enzyme functions, and disrupting mitochondrial functions. However, NO has a short half-life and is highly diffusible, so NO donors are widely used to provide NO gas molecule for antitumor treatments. NO donors can release NO on demand when stimulated by exogenous conditions such as metal ions and laser. Combining NO donors with other nanosystems to form NO delivery systems for the release of NO at specific sites is an effective strategy to exploit the anti-tumor effect of NO. This review summarizes the action mechanisms of different types of NO donors and the effects of NO delivery systems constructed using NO donors for anti-tumor therapy, and introduces the progress of NO-mediated gas therapy combined with chemodynamic therapy, photodynamic therapy, radiotherapy and chemotherapy for effective antitumor treatment, aiming to provide some theoretical reference for relevant researchers.