In Vivo Targeting through Click Chemistry. Issue 4 (20th February 2015)

• Record Type: Journal Article
• Authors: Brudno, Yevgeny; Desai, Rajiv M.; Kwee, Brian J.; Joshi, Neel S.; Aizenberg, Michael; Mooney, David J.
• Is Part Of: ChemMedChem. Volume 10:Issue 4(2015:Apr.)
• Page Start: 617
• Page End: 620
• Publication Date: 2015-02-20
• Subjects: bioorthogonal chemistry -- click chemistry -- drug delivery -- drug targeting -- gels; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402527
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Clicks degrees of separation: Selective targeting of small molecules to intramuscular and intradermal sites was achieved by click chemistry. Click‐mediated targeting gave a high degree of specificity for the target sites, and this targeting could be repeated over at least one month through nine administrations. Spatial resolution of two different molecules can be achieved by targeting them to two distinct sites in the same animal by use of orthogonal click chemistries, establishing the possibility of combining incompatible therapies in patients.