Nitrite-Responsive Hydrogel: Smart Drug Release Depending on the Severity of the Nitric Oxide-Related Disease

Nitric oxide (NO) is known as one of the most important biomarkers of many diseases. However, the development of NO-triggered drug releasing platforms is challenging due to the low concentration and short lifetime of NO in vivo. In this work, a novel nitrite (NO₂^-)-responsive hydrogel (DHPL-GEL), which can be used for smart drug release depending on the severity of the NO-related disease, is demonstrated. A dihydropyridine cross-linking agent is designed to construct DHPL-GEL to enable the responsive degradation of the hydrogel triggered by NO₂^-. On-demand release of the drug loaded in DHPL-GEL was observed under the stimulation of various concentrations of NO₂^- at the physiological level both in vitro and in vivo. In the inflammatory arthritis rat model, the DHPL-GEL drug delivery system showed a better therapeutic effect and less side effects than the traditional therapy and nonresponsive hydrogel drug delivery system, demonstrating the promising application of the NO₂^--responsive hydrogel for the treatment of NO-related diseases.