Highly Effective, Tunable, Intracellular CO Therapeutics

Description

This technology is a series of organic carbon monoxide (CO) prodrugs that release the gasotransmitter CO in a controllable fashion in response to various stimuli (pH changes, ROS, enzymes, etc.).

CO is a gasotransmitter with critical physiological functions in mammals. Its biological importance is on par with that of nitric oxide (NO), which was the subject of the 1998 Nobel Prize. CO has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis.

One major issue in developing CO based therapeutics is its delivery in a safe, pharmaceutically acceptable form. Scientists at GSU have created metal-free organic CO prodrugs, which release CO under physiological conditions with tunable rates for controlled release at a specific site or region of the body. These CO prodrugs can release CO in response to various exogenous and endogenous triggers such as water, chemical reagents, esterase, ROS, and changes in pH. This high level of controlled release allows for more precise targeting of cancer cells, reduced side effects, optimized drug delivery, and work synergistically with other treatment modalities.

Benefits

Metal-Free: Lower toxicity and immunogenicity.
Easy: No UV light activation needed so simplifies the delivery process, reduces equipment requirements, and enhances patient compliance.
Tunable: CO delivery with tunable and predictable release rates, resulting in sustained drug release and more prolonged therapeutic effect.
Stable: Extremely stable in organic solvent and can survive harsh conditions.
Controllable: Controlled release of CO in response to triggers (such as chemical reagents, ROS, and pH changes) for potentially targeted delivery.