Gram-scale preparation of quercetin supramolecular nanoribbons for intestinal inflammatory diseases by oral administration

Abstract

Gastrointestinal (GI) tract, which possesses the largest surface area of mucosa in the body, is easily suffered from inflammatory damages under the exposure of external stimulations. Excessive reactive oxygen species (ROS) production and continuous oxidative stress in intestines can elicit local mucosal injury, accelerate mucosal ulceration, and amplify the inflammatory response. Thereby, antioxidant therapy is a potential strategy against intestinal inflammatory diseases. Herein, we demonstrate the gram-scale preparation of quercetin supramolecular nanoribbons (SNRs) by using free quercetin molecules as the sole building block for preventing and treating intestinal inflammatory diseases. Unlike current clinical medicines, which mainly confront with poor response and severe adverse effects via bloodstream delivery, our quercetin SNRs possess an excellent antioxidant activity in the harsh environments of GI tract, a relative long retention time in GI tract, an admirable metabolism in GI tract without burdening other organs, and a specific adhesion to the inflamed intestinal epithelium via electrostatic interactions. These advantages strongly guarantee the applications of quercetin SNRs as oral medicines for intestinal inflammatory diseases. After establishing the models of intestinal inflammatory diseases caused by irradiation and drug stimulations, our quercetin SNRs exhibit the promising protective and therapeutic effects for radiation-induced acute enteritis and dextran sulfate sodium (DSS)-induced acute colitis. Because the super easy and fast preparation procedure and the nearly 100% loading capacity of quercetin SNRs, the current work provides a supramolecular nanomedicine with great clinical translation potential against intestinal inflammatory diseases.

Keywords: Intestinal inflammatory disease; Polyphenol; Quercetin; Self-assembly; Supramolecular nanoribbon.