Harnessing stimuli-responsive NO nanomaterials for advanced multi-disease therapy

Abstract

Nitric oxide (NO) is a critical signaling molecule with diverse physiological functions and significant therapeutic potential across various diseases. However, its clinical application faces substantial challenges due to its inherently short half-life, rapid diffusion, and potential systemic toxicity. Recent advancements in nanotechnology have enabled the development of sophisticated nanomaterials that precisely control and target NO delivery, thereby overcoming these limitations. This paper provides an in-depth review of cutting-edge NO delivery nanomaterials, emphasizing both organic and inorganic carriers engineered to respond to specific endogenous (e.g., pH, glucose, GSH, etc.) and exogenous (e.g., light, X-rays, ultrasound, etc.) stimuli. The review particularly focuses on the synergistic integration of NO therapy with other modalities such as photothermal therapy, photodynamic therapy, sonodynamic therapy, starvation therapy, immunotherapy, radiotherapy, gene therapy, chemodynamic therapy, and magnetothermal therapy. These versatile nanomaterials have shown significant efficacy in treating complex conditions, including cancer, cardiovascular disorders, inflammatory, and other diseases. Furthermore, the review discusses current challenges in NO delivery technologies, exploring the limitations and potential future developments in this field. By highlighting the latest advances, this paper underscores the promising avenues for translating NO-based therapies into clinical practice, aiming to substantially enhance therapeutic outcomes and improve patient care.