Smart Nanoplatform with Self-Stimulation Strategy for Dynamic Regulation and <i>In Situ</i> Visual Imaging of Histamine Activities in Allergic Rhinitis.

Abstract

Allergic rhinitis (AR) is a histamine-mediated upper airway inflammatory disease characterized by symptoms such as sneezing, itching, and airway hyperresponsiveness. Histamine plays a significant promoting role in the cascade reaction associated with allergic rhinitis. A promising strategy involves monitoring the severity of rhinitis through changes in histamine levels while simultaneously enabling dynamic drug release. Herein, we designed a smart nanoplatform for <i>in situ</i> visually monitoring histamine and dynamically regulating its activities with long-term treatment of AR based on mesoporous silica nanoquenchers (<i>q</i>MSNs). The mesopores of <i>q</i>MSNs were first filled by antihistamine Ketotifen (KT) and then sealed with a dye-labeled histamine aptamer. The extracellular histamine secreted from mast cells can specifically bind with its aptamer and restore the fluorescence of the aptamer along with the sustained release of the loaded drug KT. This nanoplatform was characterized by high drug-loading and an ultralow limit of detection of histamine as low as 2.49 nM. In addition, it is able to effectively release the loaded drug in a manner dependent on histamine concentration and image AR model mice's intranasal histamine levels. Based on the dual inhibition of histamine binding to its receptors by the aptamer and KT, we finally achieved an effective low-dose and long-interval drug delivery nanoplatform for improving histamine-mediated AR inflammation while enabling visual detection of intranasal histamine levels. In principle, this system could have widespread applications in respiratory allergy intervention.