PMID- 22770567 OWN - NLM STAT- MEDLINE DCOM- 20121126 LR - 20211021 IS - 1878-5905 (Electronic) IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 33 IP - 28 DP - 2012 Oct TI - In vivo targeting of alveolar macrophages via RAFT-based glycopolymers. PG - 6889-97 LID - 10.1016/j.biomaterials.2012.06.025 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Song, Eun-Ho AU - Song EH AD - Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. ehsong74@uw.edu FAU - Manganiello, Matthew J AU - Manganiello MJ FAU - Chow, Yu-Hua AU - Chow YH FAU - Ghosn, Bilal AU - Ghosn B FAU - Convertine, Anthony J AU - Convertine AJ FAU - Stayton, Partick S AU - Stayton PS FAU - Schnapp, Lynn M AU - Schnapp LM FAU - Ratner, Daniel M AU - Ratner DM LA - eng GR - K24 HL086796/HL/NHLBI NIH HHS/United States GR - R01 EB002991/EB/NIBIB NIH HHS/United States GR - R21 EB014572/EB/NIBIB NIH HHS/United States GR - K24HL068796/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120706 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Alexa Fluor 488 C5-maleimide) RN - 0 (Drug Carriers) RN - 0 (Maleimides) RN - 0 (Mannose-Binding Lectins) RN - 0 (Polymethacrylic Acids) RN - 0 (Receptors, Cell Surface) RN - 25087-26-7 (polymethacrylic acid) RN - PHA4727WTP (Mannose) RN - V956696549 (Acetylglucosamine) SB - IM MH - Acetylglucosamine/*analogs & derivatives/metabolism MH - Administration, Inhalation MH - Agglutination/drug effects MH - Analysis of Variance MH - Animals MH - Cells, Cultured MH - Drug Carriers/*administration & dosage/chemistry/metabolism MH - Macrophages, Alveolar/*metabolism MH - Maleimides/chemistry MH - Mannose/*analogs & derivatives/metabolism MH - Mannose-Binding Lectins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Polymethacrylic Acids/administration & dosage/chemical synthesis MH - Receptors, Cell Surface/*metabolism MH - Spectrophotometry, Ultraviolet PMC - PMC3449172 MID - NIHMS393362 EDAT- 2012/07/10 06:00 MHDA- 2012/12/10 06:00 PMCR- 2013/10/01 CRDT- 2012/07/10 06:00 PHST- 2012/04/09 00:00 [received] PHST- 2012/06/16 00:00 [accepted] PHST- 2012/07/10 06:00 [entrez] PHST- 2012/07/10 06:00 [pubmed] PHST- 2012/12/10 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - S0142-9612(12)00661-8 [pii] AID - 10.1016/j.biomaterials.2012.06.025 [doi] PST - ppublish SO - Biomaterials. 2012 Oct;33(28):6889-97. doi: 10.1016/j.biomaterials.2012.06.025. Epub 2012 Jul 6.