Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications

Abstract

Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a short half‐life, and its physiology role is concentration dependent, often restricting its function to a target site. Providing NO from an external source is beneficial in promoting cellular functions and treatment of different pathological conditions. Hence, the multifaceted role of NO in physiology and pathology has garnered massive interest in developing strategies to deliver exogenous NO for the treatment of various regenerative and biomedical complexities. NO‐releasing platforms or donors capable of delivering NO in a controlled and sustained manner to target tissues or organs have advanced in the past few decades. This review article discusses in detail the generation of NO via the enzymatic functions of NO synthase as well as from NO donors and the multiple biological and pathological processes that NO modulates. The methods for incorporating of NO donors into diverse biomaterials including physical, chemical, or supramolecular techniques are summarized. Then, these NO‐releasing platforms are highlighted in terms of advancing treatment strategies for various medical problems.

Light-driven micro/nanomotors in biomedical applications

“…197 NO has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). 198 H 2 S is recognized as an endogenous physiological regulator in a variety of mammalian cells and tissues. 199 Therefore, MNMs with combined photothermal and photoinduced gas propulsion can not only provide sufficient driving force but also produce gas signaling molecules with the physiological and pathological barrier weakening properties, synergistically exerting excellent ability of penetration into the deep tissue barrier and therapeutic effects on diseases.…”

Copper–Cystine Biohybrid-Embedded Nanofiber Aerogels Show Antibacterial and Angiogenic Properties

“…The origin of NO is from RSNOs (hemoglobin and albumin-based) present in human blood. NO is enzymatically produced from l -arginine by specific NOS enzymes, particularly eNOS and NOS3, generated by endothelial cells. − One of the primary concerns for NO is its stability. , Due to its high reactivity, it has a very small half-life and once synthesized, it only persists for a few milliseconds. This brief duration is insufficient to support sustained angiogenesis.…”

“…It modulates the behavior of endothelial cells by reducing apoptosis and enhancing proliferation. This effect is achieved by elevating the expression of vascular endothelial growth factor (VEGF) in areas of wounds or inflammation. ,, NO mediates podokinesis by directing the vector of VEGF, resulting in the targeted migration of endothelial cells . The most significant factor in promoting angiogenesis is the upregulation of eNOS in endothelial cells induced by the presence of NO.…”

Anti-proliferative, -migratory and -clonogenic effects of long-lasting nitric oxide release in HepG2 cells

“…10 NO has been implicated as a useful anticancer adjuvant with its involvement in oxidative stress, apoptosis, and regulation of cell cycle progression. 14 Considering these aspects, we decided to develop new scaffolds, with regulated release of NO, to ensure safe and effective therapeutic approaches with antiproliferative, -migratory and -clonogenic action (Fig. 1).…”

“…19 While various NO-donating scaffolds, such as polymeric nanoparticles, dendrimers, and silica nanoparticles, have been explored for their anticancer properties, they often exhibit shortcomings in terms of selectivity, biocompatibility, and safety concerns. 14 Given the well-documented biocompatibility of purine derivatives, we decided to build a NO-releasing compound by appropriately functionalizing the C-6 position of the purine ring with a flexible alkyl linker consisting of an O–NO 2 group (Fig. 2).…”