Peripheral Functionalization of Dendrimers Regulates Internalization and Intracellular Trafficking in Living Cells
Peripheral Functionalization of Dendrimers Regulates Internalization and Intracellular Trafficking in Living Cells
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DOI：
10.1021/bc300079h
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发表时间：
2012-05-01
影响因子：
4.7
通讯作者：
Fernandez-Megia, Eduardo
中科院分区：
文献类型：
--
作者：
Albertazzi, Lorenzo;Fernandez-Villamarin, Marcos;Fernandez-Megia, Eduardo
GATG（没食子酸-三甘醇）树枝状聚合物代表了生物医学应用的有吸引力的纳米结构。在它们的表面上掺入特异性配体和靶向及成像剂已经导致在诊断和药物递送中有前途的工具。为了进一步探索GATG树枝状聚合物在生物医学领域的多功能性，在这项工作中，我们研究了外周取代对它们在活细胞中的摄取和细胞内运输的影响。为此，具有不同的物理化学性质和生物相关性的外围组已安装在GATG树枝状聚合物的表面上，并通过共聚焦显微镜研究它们的相互作用，摄取功效和对某些细胞群体的特异性。最后，这些信息被用来设计一个pH敏感的药物递送系统，用于在溶酶体定位后在细胞内选择性释放货物分子。这些结果沿着GATG树枝状聚合物的容易功能化和模块化结构揭示了这些系统作为生物医学中有前途的纳米工具。
GATG (gallic acid-triethylene glycol) dendrimers represent appealing nanostructures for biomedical applications. The incorporation of specific ligands and targeting and imaging agents on their surface has resulted in promising tools in diagnosis and drug delivery. With the aim to further explore the versatility of GATG dendrimers in the biomedical field, in this work we study the effect of peripheral substitution on their uptake and intracellular trafficking in living cells. To this end, peripheral groups with different physicochemical properties and biological relevance have been installed on the surface of GATG dendrimers, and their interactions, uptake efficacy, and specificity for certain cell populations studied by confocal microscopy. Finally, this information was used to design a pH-sensitive drug delivery system for the selective release of cargo molecules inside cells after lysosomal localization. These results along with the easy functionalization and modular architecture of GATG dendrimers reveal these systems as promising nanotools in biomedicine.