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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
- 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.
- Subjects :
- Light
Anti-Inflammatory Agents
Serum albumin
Antineoplastic Agents
Plasma protein binding
Quinolones
010402 general chemistry
01 natural sciences
Biochemistry
Article
Catalysis
Mice
chemistry.chemical_compound
Colloid and Surface Chemistry
Human Umbilical Vein Endothelial Cells
Fluorescence microscope
Animals
Humans
Prodrugs
Cytotoxicity
A549 cell
Carbon Monoxide
biology
010405 organic chemistry
Serum Albumin, Bovine
General Chemistry
Prodrug
Combinatorial chemistry
0104 chemical sciences
RAW 264.7 Cells
chemistry
A549 Cells
Cancer cell
biology.protein
Cattle
Protein Binding
Carbon monoxide
Subjects
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