Visible-Light-Activated Quinolone Carbon-Monoxide-Releasing Molecule: Prodrug and Albumin-Assisted Delivery Enables Anticancer and Potent Anti-Inflammatory Effects

Authors:
Publisher website
Google Scholar
Abstract
The delivery of controlled amounts of carbon monoxide (CO) to biological targets is of significant current interest. Very few CO-releasing compounds are currently known that can be rigorously controlled in terms of the location and amount of CO released. To address this deficiency, we report herein a new metal-free, visible light-induced CO-releasing molecule (photoCORM) and its prodrug oxidized form, which offer new approaches to controlled, localized CO-delivery. The new photoCORM, based on a 3-hydroxybenzo[g]quinolone framework, releases one equivalent of CO upon visible light illumination under a variety of biologically-relevant conditions. This non-toxic compound can be tracked prior to CO release using fluorescence microscopy and produces a non-toxic byproduct following CO release. An oxidized prodrug form of the photoCORM is reduced by cellular thiols, providing an approach toward activation in the reducing environment of cancer cells. Strong non-covalent affinity of the non-metal photoCORM to albumin enables use of an albumin:photoCORM complex for targeted CO delivery to cancer cells. This approach produced cytotoxicity IC50 values among the lowest reported to date for CO delivery to cancer cells by a photoCORM. This albumin:photoCORM complex is also the first CO delivery system to produce significant anti-inflammatory effects when introduced at nanomolar photoCORM concentration.
Funding Information
  • Division of Chemistry (CHE-1429195)
  • Directorate for Mathematical and Physical Sciences (CHE-1301092)
  • Utah Agricultural Experiment Station (UTA-01178)
  • National Institute of General Medical Sciences (R15GM124596)
  • Utah State University Office of Research and Graduate Studies

This publication has 62 references indexed in Scilit: