In vivo targeting of alveolar macrophages via RAFT-based glycopolymers.
In vivo targeting of alveolar macrophages via RAFT-based glycopolymers.
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DOI：
10.1016/j.biomaterials.2012.06.025
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发表时间：
2012-10
期刊：
影响因子：
14
通讯作者：
Ratner, Daniel M.
中科院分区：
文献类型：
--
作者：
Song, Eun-Ho;Manganiello, Matthew J.;Chow, Yu-Hua;Ghosn, Bilal;Convertine, Anthony J.;Stayton, Partick S.;Schnapp, Lynn M.;Ratner, Daniel M.
通过内源性碳水化合物受体靶向细胞群体是一种有吸引力的药物递送方法。然而，为了有效，这种策略需要生产能够与特定细胞表面凝集素结合的高亲和力碳水化合物配体。为了开发对这些受体表现出高亲和力的材料，我们通过可逆加成-断裂链转移（RAFT）聚合从碳水化合物官能化的单体前体合成了显示悬垂碳水化合物部分的糖共聚物。这些糖聚合物被荧光标记，并用于确定巨噬细胞特异性靶向在体外和体内。与含半乳糖的糖聚合物相比，含甘露糖和N-乙酰葡糖胺的糖聚合物在体外以剂量依赖性方式特异性靶向小鼠骨髓源性巨噬细胞（BMDM）（摄取分别高出30倍和19倍）。此外，在巨噬细胞分化后，甘露糖糖共聚物在M2极化巨噬细胞中表现出增强的摄取，M2极化巨噬细胞是损伤组织中普遍存在的抗炎巨噬细胞表型。这种碳水化合物特异性摄取保留在体内，因为肺泡巨噬细胞表现出6倍更高的内化甘露糖糖共聚物相比，半乳糖，小鼠体内给药后。我们已经成功地合成了一类功能性RAFT glycopolymers，能够在体外和体内巨噬细胞型特异性摄取，对未来靶向药物递送系统的设计具有重要意义。
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 pendant 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.
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影响因子：
6.2
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