Cell-specific gene transfection from a gene-functionalized poly(D,L-lactic acid) substrate fabricated by the layer-by-layer assembly technique

Cell-specific gene transfection from a gene-functionalized poly(D,L-lactic acid) substrate fabricated by the layer-by-layer assembly technique
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通过层层组装技术制造的基因功能化聚(D,L-乳酸)基质进行细胞特异性基因转染

DOI:
10.1002/anie.200800412
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发表时间:
2008-01-01
影响因子:
16.6
通讯作者:
Deng, Linhong
Deng, Linhong
中科院分区:
化学1区
文献类型:
--
作者:
Cai, Kaiyong;Hu, Yan;Deng, Linhong

文献摘要

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受控和有效的基因递送/转染在许多重要的生物医学应用中是必不可少的。这一过程受到细胞微环境的高度调节。[1]以前已经采用了各种策略[2,3]来递送基因,但这些策略仅取得了有限的成功。[4]然而,这可能通过材料表面诱导的基因递送/转染来改善。[4,5-7]例如,货车den Beucken等人证明了DNA-聚合物分层膜可用于生物医学应用。[7]然而,这些报告都没有建立细胞特异性识别和材料表面上的基因转染。在此,我们提出了一种方法来制造基因标记的聚(d,l-乳酸)(PDLLA)基板,显示出潜在的细胞特异性识别和连续的界面传递质粒DNA的材料的表面。我们的方法涉及形成纳米结构的,成对的多层半乳糖基化壳聚糖和质粒DNA的PDLLA膜通过使用逐层(LBL)组装技术。该技术基于聚阴离子和聚阳离子通过静电相互作用的顺序吸附。它允许生物材料的功能化,以控制细胞活性和局部递送药物。[8,9]我们在此提出的结果可能在组织工程、[10]细胞/基因刺激生物材料的开发、[11]基因治疗、[3,9]和植入技术中具有广泛的应用。[12个]
Controlled and efficient gene delivery/transfection is essential in many important biomedical applications. This process is highly regulated by the cellular microenvironment.[1] Various strategies [2, 3] have previously been employed to deliver genes, but these achieved only limited success.[4] However, this might be improved with gene delivery/transfection induced by a material s surface.[4, 5–7] For example, van den Beucken et al. demonstrated that a DNA–polymer layered film can be used for biomedical applications.[7] Nevertheless, none of these reports established both cell-specific recognition and gene transfection on the surface of a material. Herein, we present a method to fabricate gene-tagged poly (d, l-lactic acid)(PDLLA) substrates that show potential for both cell-specific recognition and continuous interfacial delivery of plasmid DNA by a material s surface. Our approach involves the formation of nanostructured, paired multilayers of galactosylated chitosan and plasmid DNA on PDLLA films by using the layer-by-layer (LbL) assembly technique. This technique is based on the sequential adsorption of polyanions and polycations through electrostatic interactions. It allows the functionalization of biomaterials both to control cell activity and to deliver drugs locally.[8, 9] The results we present herein may have wide applications in tissue engineering,[10] the development of cell-/gene-stimulating biomaterials,[11] gene therapy,[3, 9] and implant technology.[12]