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聚磷酸酯表面活性剂作为聚合物纳米载体的通用隐形涂层

Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers.

作者信息

Bauer Kristin N, Simon Johanna, Mailänder Volker, Landfester Katharina, Wurm Frederik R

机构信息

Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.

Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany; Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.

出版信息

Acta Biomater. 2020 Oct 15;116:318-328. doi: 10.1016/j.actbio.2020.09.016. Epub 2020 Sep 13.

Abstract

Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with different binding motifs were synthesized by anionic ring-opening polymerization of cyclic phosphates or phosphonates and well-defined polymers were obtained. They were evaluated with regard to their cytotoxicity, protein interactions, and corona formation and their cellular uptake. We proved that all PPE-surfactants have lower cytotoxicity as the common PEG-based surfactant (Lutensol® AT 50) and that their hydrolysis is controlled by their chemical structure. Two polymeric nanocarriers, namely polystyrene and poly(methyl methacrylate), and bio-based and potentially biodegradable hydroxyethyl starch nanocarriers were coated with the PPE-surfactants. All nanocarriers exhibited reduced protein adsorption after coating with PPE-surfactants and a strongly reduced interaction with macrophages. This general strategy allows the transformation of polymeric nanocarriers into camouflaged nanocarriers and by the chemical versatility of PPEs will allow the attachment of additional moieties for advanced drug delivery.

摘要

纳米载体的调理作用是控释药物递送中最重要的生物屏障之一。防止这种非特异性蛋白质吸附从而避免被免疫系统快速清除的典型方法是用聚乙二醇(PEG)对药物递送载体进行共价修饰,即所谓的聚乙二醇化。最近,聚磷酸酯(PPE)被确定为合适的PEG替代物,但其具有可控亲水性、额外化学功能或可生物降解性等优点。在此,我们提出一种通过将不同的非离子型PPE表面活性剂非共价吸附到具有隐身特性的纳米载体上的通用策略。通过环状磷酸盐或膦酸盐的阴离子开环聚合合成了具有不同结合基序的聚磷酸酯表面活性剂,并获得了结构明确的聚合物。对它们的细胞毒性、蛋白质相互作用、冠层形成及其细胞摄取进行了评估。我们证明,所有PPE表面活性剂的细胞毒性都低于常见的基于PEG的表面活性剂(Lutensol® AT 50),并且它们的水解受其化学结构控制。两种聚合物纳米载体,即聚苯乙烯和聚(甲基丙烯酸甲酯),以及生物基且可能可生物降解的羟乙基淀粉纳米载体都用PPE表面活性剂进行了包覆。所有纳米载体在用PPE表面活性剂包覆后蛋白质吸附减少,与巨噬细胞的相互作用也大大降低。这种通用策略可将聚合物纳米载体转变为伪装纳米载体,并且通过PPE的化学多功能性将允许连接额外的基团用于先进的药物递送。

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