Reversing the Cytotoxicity of Bile Acids by Supramolecular Encapsulation
Authors:
- 18 April 2017
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 60 (8) , 3266-3274
Abstract
Supramolecular encapsulation has been developed into a powerful tool in clearance of toxic substances and hazardous waste from living body and external environments. Herein we tested the special efficacy of tyramine-modified β-cyclodextrin (1) in inhibiting and reversing of the inherent cytotoxicity of deoxycholic acid (DCA). The decarboxylation from tyrosine to tyramine in 1 is crucial to the mutual electrostatic communication, ultimately leading to great enhancement in binding affinity and molecular selectivity toward bile acids. As a result, the DCA-mediated cytotoxicity could be largely eliminated by the biocompatible 1. Meanwhile, the excess DCA could be rapidly excreted by 1 via rat urinary clearance, thus facilitating the decrease of DCA concentration in blood. This study presents a proof of principle that the supramolecular encapsulation with functional cyclodextrin derivatives can efficiently modulate the cell progression and remove the cytotoxic DCA, which provides a practical approach to prevent or treat bile acid-involved diseases.Keywords
Funding Information
- National Natural Science Foundation of China (21432004, 21472100, 91527301)
This publication has 30 references indexed in Scilit:
- Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and ApplicationsJournal of the American Chemical Society, 2016
- Dramatically Promoted Swelling of a Hydrogel by Pillar[6]arene–Ferrocene Complexation with Multistimuli ResponsivenessJournal of the American Chemical Society, 2016
- Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced ToxicityPLOS ONE, 2016
- New Frontiers for Encapsulation in the Chemical IndustryACS Applied Materials & Interfaces, 2015
- A weighted relative difference accumulation algorithm for dynamic metabolomics data: long-term elevated bile acids are risk factors for hepatocellular carcinomaScientific Reports, 2015
- Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasisToxicology and Applied Pharmacology, 2015
- Supramolecular cyclodextrin-based drug nanocarriersChemical Communications, 2015
- Three-dimensional periodic supramolecular organic framework ion sponge in water and microcrystalsNature Communications, 2014
- Biomedical Applications of Supramolecular Systems Based on Host–Guest InteractionsChemical Reviews, 2014
- Host–Guest Supramolecular Nanosystems for Cancer Diagnostics and TherapeuticsAdvanced Materials, 2013