title: In vivo targeting through click chemistry.
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.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Cir., Boston, MA 02115 (USA); School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138 (USA).
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Brudno
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Desai
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Kwee
authors.forename: Neel S
authors.initials: NS
authors.lastname: Joshi
authors.forename: Michael
authors.initials: M
authors.lastname: Aizenberg
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000464:Alginates / Q000737:chemistry; D000480:Alkynes / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001386:Azides; D001555:Benzene Derivatives / Q000008:administration & dosage* / Q000737:chemistry; D057930:Click Chemistry / Q000379:methods*; D034242:Cyclooctanes / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D051379:Mice; D009132:Muscles / Q000378:metabolism*
chemical_list: D000464:Alginates; D000480:Alkynes; D001386:Azides; D001555:Benzene Derivatives; D034242:Cyclooctanes; D005456:Fluorescent Dyes; D006573:Heterocyclic Compounds, 1-Ring; D006603:Hexuronic Acids; D020100:Hydrogels; C000598289:tetrazine dye 10; C042001:1-octyne; D020723:Glucuronic Acid
keywords: bioorthogonal chemistry; click chemistry; drug delivery; drug targeting; gels