title: In vivo targeting of alveolar macrophages via RAFT-based glycopolymers.
abstract: Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendent carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization. These glycopolymers were fluorescently labeled and used to determine macrophage-specific targeting both in vitro and in vivo. Mannose- and N-acetylglucosamine-containing glycopolymers were shown to specifically target mouse bone marrow-derived macrophages (BMDMs) in vitro in a dose-dependent manner as compared to a galactose-containing glycopolymer (30- and 19-fold higher uptake, respectively). In addition, upon macrophage differentiation, the mannose glycopolymer exhibited enhanced uptake in M2-polarized macrophages, an anti-inflammatory macrophage phenotype prevalent in injured tissue. This carbohydrate-specific uptake was retained in vivo, as alveolar macrophages demonstrated 6-fold higher internalization of mannose glycopolymer, as compared to galactose, following intratracheal administration in mice. We have shown the successful synthesis of a class of functional RAFT glycopolymers capable of macrophage-type specific uptake both in vitro and in vivo, with significant implications for the design of future targeted drug delivery systems.
authors: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. ehsong74@uw.edu
authors: Eun-Ho
authors: EH
authors: Song
authors: Matthew J
authors: MJ
authors: Manganiello
authors: Yu-Hua
authors: YH
authors: Chow
authors: Bilal
authors: B
authors: Ghosn
authors: Anthony J
authors: AJ
authors: Convertine
authors: Partick S
authors: PS
authors: Stayton
authors: Lynn M
authors: LM
authors: Schnapp
authors: Daniel M
authors: DM
authors: Ratner
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000378:metabolism; D000280:Administration, Inhalation; D000371:Agglutination / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008301:Maleimides / Q000737:chemistry; D008358:Mannose / Q000031:analogs & derivatives* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000138:chemical synthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C504424:Alexa Fluor 488 C5-maleimide; D004337:Drug Carriers; D008301:Maleimides; D037241:Mannose-Binding Lectins; D011109:Polymethacrylic Acids; D011956:Receptors, Cell Surface; C030613:polymethacrylic acid; D008358:Mannose; D000117:Acetylglucosamine