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用于药物和基因递送的生物工程化弹性蛋白和丝素生物材料。

Bioengineered elastin- and silk-biomaterials for drug and gene delivery.

机构信息

Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.

Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA.

出版信息

Adv Drug Deliv Rev. 2020;160:186-198. doi: 10.1016/j.addr.2020.10.008. Epub 2020 Oct 17.

Abstract

Advances in medical science have led to diverse new therapeutic modalities, as well as enhanced understanding of the progression of various disease states. These findings facilitate the design and development of more customized and exquisite drug delivery systems that aim to improve therapeutic indices of drugs to treat a variety of conditions. Synthetic polymer-based drug carriers have often been the focus of such research. However, these structures suffer from challenges with heterogeneity of the starting material, limited chemical features, complex functionalization methods, and in some cases a lack of biocompatibility. Consequently, protein-based polymers have garnered much attention in recent years due to their monodisperse features, ease of production and functionalization, and biocompatibility. Genetic engineering techniques enable the advancement of protein-based drug delivery systems with finely tuned physicochemical properties, and thus an expanded level of customization unavailable with synthetic polymers. Of these genetically engineered proteins, elastin-like proteins (ELP), silk-like proteins (SLP), and silk-elastin-like proteins (SELP) provide a unique set of alternatives for designing drug delivery systems due to their inherent chemical and physical properties and ease of engineering afforded by recombinant DNA technologies. In this review we examine the advantages of genetically engineered drug delivery systems with emphasis on ELP and SLP constructions. Methods for fabrication and relevant biomedical applications will also be discussed.

摘要

医学科学的进步带来了多样化的新治疗模式,以及对各种疾病状态进展的更深入理解。这些发现促进了更具针对性和更精致的药物输送系统的设计和开发,旨在提高治疗各种疾病的药物的治疗指数。基于合成聚合物的药物载体一直是此类研究的重点。然而,这些结构存在起始材料不均匀、化学性质有限、功能化方法复杂以及在某些情况下缺乏生物相容性等问题。因此,近年来,由于其单分散性、易于生产和功能化以及生物相容性,基于蛋白质的聚合物受到了广泛关注。遗传工程技术使基于蛋白质的药物输送系统能够具有精细调节的物理化学性质,从而实现了合成聚合物无法实现的扩展定制水平。在这些基因工程蛋白中,弹性蛋白样蛋白(ELP)、丝蛋白样蛋白(SLP)和丝弹性蛋白样蛋白(SELP)由于其固有化学和物理性质以及重组 DNA 技术提供的易于工程化的特性,为设计药物输送系统提供了独特的选择。在这篇综述中,我们检查了基因工程药物输送系统的优势,重点介绍了 ELP 和 SLP 结构。还将讨论制造方法和相关的生物医学应用。

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