Noncovalent cell surface engineering with cationic graft copolymers.

Noncovalent cell surface engineering with cationic graft copolymers.
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DOI:
10.1021/ja908887v
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发表时间:
2009-12
影响因子:
15
通讯作者:
John T. Wilson;Venkata R. Krishnamurthy;W. Cui;Z. Qu;E. Chaikof
John T. Wilson;Venkata R. Krishnamurthy;W. Cui;Z. Qu;E. Chaikof
中科院分区:
化学1区
文献类型:
--
作者:
John T. Wilson;Venkata R. Krishnamurthy;W. Cui;Z. Qu;E. Chaikof

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细胞表面工程的化学方法已成为重塑细胞和组织分子景观的强大工具。在这里,我们报告了一种通过将适当结构和功能化的聚(L-赖氨酸)-接枝-聚(乙二醇)(PLL-g-PEG)共聚物静电吸附到细胞界面来重新设计细胞表面的新策略。将甲氧基封端的四(乙二醇)链接枝到 PLL 上,以电荷密度和 PEG 依赖性方式消除了聚阳离子细胞毒性,并且具有接枝 PEG 链和吸附到细胞表面的游离赖氨酸单体的独特平衡结构的共聚物,且不影响活力。结构类似的带有末端功能化 PEG 接枝物的 PLL-g-PEG 共聚物被用作生物素、酰肼和叠氮化物部分的“细胞表面活性”聚合物载体,它们分别选择性地捕获细胞表面上的链霉亲和素、醛和环辛炔标记的探针。该策略为细胞表面工程开辟了新的机遇,包括生成独特的细胞表面图案、快速组合表面修饰以及生物复杂溶剂的使用。定制的 PLL-g-PEG 共聚物为生物/化学重塑细胞和组织提供了一种有前途且可行的工具,在生物医学和生物技术应用中具有广泛的潜力。
Chemical approaches to cell surface engineering have emerged as powerful tools for resurfacing the molecular landscape of cells and tissues. Here we report a new strategy for re-engineering cell surfaces through electrostatic adsorption of appropriately structured and functionalized poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) copolymers to cellular interfaces. Grafting of methoxy terminated tetra(ethylene glycol) chains to PLL abrogated polycation cytotoxicity in a charge density and PEG dependent manner, and copolymers structured with a unique balance of grafted PEG chains and free lysine monomers adsorbed to cell surfaces without compromising viability. Structurally analogous PLL-g-PEG copolymers bearing terminally functionalized PEG grafts were used as 'cell surface active' polymeric carriers for biotin, hydrazide, and azide moieties, which selectively captured streptavidin-, aldehyde-, and cyclooctyne-labeled probes, respectively, on cell surfaces. This strategy opens new opportunities in cell surface engineering, including generation of unique cell surface motifs, rapid and combinatorial surface modification, and use of biologically complex solvents. Tailored PLL-g-PEG copolymers offer a promising and enabling tool for bio/chemically remodeling cells and tissues with broad potential in biomedical and biotechnological applications.