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自组装 Janus 树状大分子的模块化合成及载药树状大分子囊泡的简便制备。

Modular synthesis of self-assembling Janus-dendrimers and facile preparation of drug-loaded dendrimersomes.

机构信息

Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University, FI-00076, Finland.

出版信息

Nanoscale. 2017 Jun 1;9(21):7189-7198. doi: 10.1039/c6nr08102a.

Abstract

Materials and methods aimed at the next generation of nanoscale carriers for drugs and other therapeutics are currently in great demand. Yet, creating these precise molecular arrangements in a feasible and straightforward manner represents a remarkable challenge. Herein we report a modular synthetic route for amphiphilic Janus-dendrimers via a copper-catalyzed click reaction (CuAAC) and a facile procedure, using simple injection, to obtain highly uniform dendrimersomes with efficient loading of the model drug compound propranolol. The resulting assemblies were analyzed by dynamic light scattering and cryogenic transmission electron microscopy revealing the formation of unilamellar and multilamellar dendrimersomes. The formation of a bilayer structure was confirmed using cryo-TEM and confocal microscopy visualization of an encapsulated solvatochromic dye (Nile Red). The dendrimersomes reported here are tunable in size, stable over time and display robust thermal stability in aqueous media. Our results expand the scope of dendrimer-based supramolecular colloidal systems and offer the means for one-step fabrication of drug-loaded dendrimersomes in the size range of 90-200 nm, ideal for biomedical applications.

摘要

目前,人们对下一代用于药物和其他治疗方法的纳米级载药系统的需求很大。然而,以可行且直接的方式来构建这些精确的分子排列结构极具挑战性。在此,我们通过铜催化点击反应(CuAAC)和简单的注射方法报道了一种两亲性Janus 树状大分子的模块化合成途径,可获得具有高效负载模型药物普罗帕酮的高度均一的树枝状囊泡。通过动态光散射和低温透射电子显微镜对所得组装体进行分析,结果表明形成了单分子层和多分子层的树枝状囊泡。使用冷冻 TEM 和包封溶剂致变色染料(Nile Red)的共聚焦显微镜可视化证实了双层结构的形成。这里报道的树枝状囊泡可调节尺寸,随时间稳定,并在水介质中显示出稳健的热稳定性。我们的结果扩展了基于树枝状大分子的超分子胶体系统的范围,并提供了在 90-200nm 尺寸范围内一步制备载药树枝状囊泡的方法,非常适合生物医学应用。

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