Abstract
Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery. Drug-eluting devices implanted during invasive surgery allow the controlled presentation of drugs at the disease site, but cannot be modified once the surgery is complete. We demonstrate that bioorthogonal click chemistry can be used to target circulating small molecules to hydrogels resident intramuscularly in diseased tissues. We also demonstrate that small molecules can be repeatedly targeted to the diseased area over the course of at least one month. Finally, two bioorthogonal reactions were used to segregate two small molecules injected as a mixture to two separate locations in a mouse disease model. These results demonstrate that click chemistry can be used for pharmacological drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.
Highlights
Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery
One approach to target implanted devices is to modify them with molecular targets capable of recognizing and binding small molecules circulating in the body
Fluorescent DBCO bound alginate-azide gels while demonstrating little interaction with unmodified alginate gels (Figure 1B). It was investigated whether small molecules labeled with near-IR (NIR) fluorophores could target in vivo to gels resident at a disease site in an animal model of lower limb ischemia. 50 μL of tetrazine-modified, azide-modified, or unmodified alginate gels intra-muscular gel DN N +
Summary
Targeting small molecules to diseased tissues as therapy or diagnosis is a significant challenge in drug delivery. We report the utilization of bioorthogonal click chemistry to accumulate small molecules at a site of animal injury. Drug payloads circulating in the blood of a patient could be bound by the device though specific chemical recognition, allowing for subsequent release through low-pH-mediated hydrolysis[8] or enzymatic degradation[9] at the target site.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
