Back to Search Start Over

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

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

Authors :
Tatiana Soboleva
Lisa M. Berreau
Suliman Ayad
Marina Popova
Abby D. Benninghoff
Source :
Journal of the American Chemical Society. 140:9721-9729
Publication Year :
2018
Publisher :
American Chemical Society (ACS), 2018.

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 IC(50) 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.

Details

ISSN :
15205126 and 00027863
Volume :
140
Database :
OpenAIRE
Journal :
Journal of the American Chemical Society
Accession number :
edsair.doi.dedup.....0daf32389ab5d8bc7b66506662fda91c
Full Text :
https://doi.org/10.1021/jacs.8b06011