Tuning Cellular Biological Functions Through the Controlled Release of NO from a Porous Ti-MOF

Angew Chem Int Ed Engl. 2020 Mar 23;59(13):5135-5143. doi: 10.1002/anie.201913135. Epub 2020 Feb 20.

Abstract

Materials for the controlled release of nitric oxide (NO) are of interest for therapeutic applications. However, to date, many suffer from toxicity and stability issues, as well as poor performance. Herein, we propose a new NO adsorption/release mechanism through the formation of nitrites on the skeleton of a titanium-based metal-organic framework (MOF) that we named MIP-177, featuring a suitable set of properties for such an application: (i) high NO storage capacity (3 μmol mg-1solid ), (ii) excellent biocompatibility at therapeutic relevant concentrations (no cytotoxicity at 90 μg mL-1 for wound healing) due to its high stability in biological media (<9 % degradation in 72 hours) and (iii) slow NO release in biological media (≈2 hours for 90 % release). The prospective application of MIP-177 is demonstrated through NO-driven control of mitochondrial respiration in cells and stimulation of cell migration, paving the way for the design of new NO delivery systems for wound healing therapy.

Keywords: IR spectroscopy; metal-organic frameworks; modelling; nitric oxide; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Biocompatible Materials / chemistry*
  • Cell Physiological Phenomena / drug effects
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Metal-Organic Frameworks / chemistry*
  • Nitric Oxide / chemistry*
  • Nitric Oxide / pharmacology*
  • Porosity
  • Titanium / chemistry*
  • Wound Healing / drug effects

Substances

  • Biocompatible Materials
  • Delayed-Action Preparations
  • Drug Carriers
  • Metal-Organic Frameworks
  • Nitric Oxide
  • Titanium