由于其生物相容性,多肽在纳米医学中显示出优异的潜力,生物降解性,高功能性,和对几种刺激的反应。多肽在超分子水平上表现出很高的组织倾向;因此,它们已被广泛认为是逐层(LbL)组装中的构建块。LBL技术是一种高度通用的方法,这涉及到构建块的顺序组装,主要由静电相互作用驱动,在平面或胶体模板上制造复杂的多层纳米结构。LbL方法所需的简单性和温和条件导致包含生物聚合物和生物活性分子,用于制造广谱的生物可降解物质,生物相容性以及用于生物医学应用的精确设计的多层薄膜。这篇综述集中在这些例子中,多肽已被用作多层纳米结构的构建块,用于组织工程和药物递送应用。强调多肽的特性和增加多层膜稳定性的策略。交联是增强多层网络的稳定性和刚度的有力策略。这是生物医学应用的基本要求。例如,在组织工程学中,坚硬的多层涂层,粘合促进剂的存在,和/或生物活性分子增强粘附力,增长,和细胞的分化。相反,抗菌涂料应排斥和抑制细菌的生长。在药物输送应用中,主要集中在微米和纳米尺度的颗粒和胶囊,多层膜的稳定性在有效负载的保留和受控释放方面是至关重要的。最近的进展表明,多肽在高负载效率的遗传物质吸附中的关键作用,以及在细胞内摄取过程中解决颗粒/胶囊的不同途径,为个性化医疗的应用铺平了道路。虽然有一些研究,多肽对pH变化的响应性,以及将刺激响应实体包含到多层网络中,代表了智能药物输送系统的发展,以促进治疗持续释放的另一个关键因素。一旦施加外部刺激,多肽的降解性在某些情况下可能是药物的受控细胞内释放的障碍。如今,可生物降解的LbL颗粒/胶囊的高度工程化设计是以治疗的发展为导向的,限于使用多肽,他们还处于婴儿期。
Polypeptides have shown an excellent potential in nanomedicine thanks to their biocompatibility, biodegradability, high functionality, and responsiveness to several stimuli. Polypeptides exhibit high propensity to organize at the supramolecular level; hence, they have been extensively considered as building blocks in the layer-by-layer (LbL) assembly. The LbL technique is a highly versatile methodology, which involves the sequential assembly of building blocks, mainly driven by electrostatic interactions, onto planar or colloidal templates to fabricate sophisticated multilayer nanoarchitectures. The simplicity and the mild conditions required in the LbL approach have led to the inclusion of biopolymers and bioactive molecules for the fabrication of a wide spectrum of biodegradable, biocompatible, and precisely engineered multilayer films for biomedical applications. This review focuses on those examples in which polypeptides have been used as building blocks of multilayer nanoarchitectures for tissue engineering and drug delivery applications, highlighting the characteristics of the polypeptides and the strategies adopted to increase the stability of the multilayer film. Cross-linking is presented as a powerful strategy to enhance the stability and stiffness of the multilayer network, which is a fundamental requirement for biomedical applications. For example, in tissue engineering, a stiff multilayer coating, the presence of adhesion promoters, and/or bioactive molecules boost the adhesion, growth, and differentiation of cells. On the contrary, antimicrobial coatings should repel and inhibit the growth of bacteria. In drug delivery applications, mainly focused on particles and capsules at the micro- and nano-meter scale, the stability of the multilayer film is crucial in terms of retention and controlled release of the payload. Recent advances have shown the key role of the polypeptides in the adsorption of genetic material with high loading efficiency, and in addressing different pathways of the particles/capsules during the intracellular uptake, paving the way for applications in personalized medicine. Although there are a few studies, the responsiveness of the polypeptides to the pH changes, together with the inclusion of stimuli-responsive entities into the multilayer network, represents a further key factor for the development of smart drug delivery systems to promote a sustained release of therapeutics. The degradability of polypeptides may be an obstacle in certain scenarios for the controlled intracellular release of a drug once an external stimulus is applied. Nowadays, the highly engineered design of biodegradable LbL particles/capsules is oriented on the development of theranostics that, limited to use of polypeptides, are still in their infancy.