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Updated: Jan 29, 2026
Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Free radical-mediated targeting and immobilization of coupled payloads
Christopher J Lowe1, Emily T DiMartini1, Keana R Mirmajlesi1
1a Department of Biomedical Engineering, Rutgers, The State University of New Jersey , Piscataway , NJ , USA.
Abstract:
Targeted drug delivery is a promising approach to enhance the accumulation of therapies in diseased tissues while limiting off-site effects. Ligand-receptor interactions are traditionally identified to deliver therapies, and although specific, this can be costly and often suffers from limited sensitivity. An emerging approach is to target intermediary species that modulate disease progression. Here, we propose novel methods of targeting therapies by using native free radicals as a homing signal. Elevated concentrations of free radicals are a characteristic comorbidity of many different diseases. In polymer chemistry, free radicals are frequently used to initiate crosslinking reactions. We proposed that free radicals elevated in injury sites are capable of inducing crosslinking of acrylate groups on polymer chains. Coupling payloads to the polymer then allow for specific targeting of therapies to areas with elevated free radicals. We demonstrate in vitro proof-of-principle of this approach. Reactive oxygen species (ROS) initiated crosslinking of acrylated PEGs, which immobilized a fluorescent payload within tissue mimics. The cross-linking efficiency and immobilization potential varied with the polymer chain length, suggesting that a tuneable platform can be achieved. Together these results provide promising proof-of-concept for using free radicals to specifically target and sustain nearly endless payloads to disease sites.
Insights
This study introduces a novel targeted therapy approach using free radicals as homing signals. This method leverages elevated free radical concentrations at disease sites to crosslink polymers, enabling specific drug delivery and reducing side effects.
Area of Science:
- Biomedical Engineering
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Targeted drug delivery aims to increase therapy concentration in diseased tissues and minimize off-site effects.
- Traditional ligand-receptor targeting is specific but costly and lacks sensitivity.
- Free radicals, elevated in many diseases, can be leveraged as a novel targeting mechanism.
Purpose of the Study:
- To develop and demonstrate a novel therapeutic targeting strategy using native free radicals as homing signals.
- To investigate the use of free radicals to initiate polymer crosslinking for targeted drug delivery.
- To establish proof-of-concept for a free radical-activated polymer platform for disease site-specific therapy.
Main Methods:
- Proposed using elevated free radicals at injury sites to induce crosslinking of acrylate groups on polymer chains.
- Coupled therapeutic payloads to polymer chains for targeted delivery.
- Demonstrated *in vitro* proof-of-principle using reactive oxygen species (ROS) to initiate crosslinking of acrylated polyethylene glycols (PEGs).
Main Results:
- Reactive oxygen species (ROS) successfully initiated crosslinking of acrylated PEGs.
- Immobilization of a fluorescent payload within tissue mimics was achieved via crosslinking.
- Cross-linking efficiency and payload immobilization varied with polymer chain length, indicating a tuneable platform.
Conclusions:
- Free radicals can be effectively utilized as homing signals for targeted therapy delivery.
- The proposed polymer crosslinking approach shows promise for specific drug targeting to disease sites.
- This platform offers a tuneable and potentially cost-effective method for sustained payload delivery to pathological areas.
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