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基于 Triton-X 家族表面活性剂的自组装胶束簇,用于增强增溶、包封、蛋白质通透性控制和抗癌药物递送。

Self-assembled micellar clusters based on Triton-X-family surfactants for enhanced solubilization, encapsulation, proteins permeability control, and anticancer drug delivery.

机构信息

Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology, 7 Sheremetevskij prospect, Ivanovo 153000, Russian Federation.

Inorganic Chemistry Department, Ivanovo State University of Chemistry and Technology, 7 Sheremetevskij prospect, Ivanovo 153000, Russian Federation.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Jun;99:794-804. doi: 10.1016/j.msec.2019.02.016. Epub 2019 Feb 8.

DOI:10.1016/j.msec.2019.02.016
PMID:30889754
Abstract

Non-ionic surfactants have raised a considerable interest for solubilization, encapsulation, permeabilization and controlled release of various compounds due to their unique physicochemical properties. Nevertheless, it is still challenging to create convenient self-assembled multifunctional materials with high solubilization and encapsulation capacities by preserving their advanced capabilities to protect loaded cargos without altering their characteristics. In this work, we present an extended concept of micellar clusters (MCs) formation based on partial entrapment and stabilization of chelate ligands by hydrophobic forces found on the non-ionic surfactant micelle interface of the Triton-X family (TX-100/TX-114), followed by subsequent complexation of the preformed structures either by metal ions or a supporting chelator. The formation aspects, inner structure and the role of external factors such as the addition of competitive ligands have been extensively studied. MCs loaded by hydrophobic fluorescent compounds with high encapsulation efficiency demonstrate an excellent optical response in aqueous media without crystallization as well as sufficient increase in solubility of toxic hydrophobic compounds such as bilirubin (>50 times compared to pure surfactants). Furthermore, Triton-X-based MCs provide a unique feature of selective permeability to hydrophilic ligand-switching proteins such as UnaG and BSA demonstrating bright "turn-on" fluorescence signal either inside the cluster or on its interface via complexation. The proposed strategies allowed us to successfully encapsulate and visualize a newly synthesized, highly hydrophobic anticancer PTR-58-CLB-CAMP peptide drug, while MCs loaded by the drug exhibit a considerable antitumor activity against HeLa cells.

摘要

由于具有独特的物理化学性质,非离子型表面活性剂在增溶、包封、渗透和控制各种化合物的释放方面引起了相当大的兴趣。然而,通过保留其保护负载货物的先进能力而不改变其特性,仍然难以创建具有高增溶和包封能力的方便的自组装多功能材料。在这项工作中,我们提出了基于部分捕获和稳定螯合剂配体的胶束簇 (MC) 形成的扩展概念,这是通过疏水力实现的,疏水力存在于 Triton-X 系列 (TX-100/TX-114) 的非离子表面活性剂胶束界面上,然后通过金属离子或支持螯合剂对预形成的结构进行后续络合。我们广泛研究了形成方面、内部结构以及外部因素(如添加竞争配体)的作用。用高封装效率的疏水性荧光化合物负载的 MC 证明了在水介质中具有出色的光学响应,而不会结晶,并且疏水性有毒化合物如胆红素的溶解度也有足够的提高(与纯表面活性剂相比提高了 50 倍以上)。此外,基于 Triton-X 的 MC 提供了亲水配体切换蛋白(如 UnaG 和 BSA)选择性渗透的独特特性,通过络合,无论是在簇内还是在其界面上,都可以显示出明亮的“开启”荧光信号。所提出的策略使我们能够成功地封装和可视化新合成的、高度疏水性的抗癌 PTR-58-CLB-CAMP 肽药物,而负载药物的 MC 对 HeLa 细胞表现出相当大的抗肿瘤活性。

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