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多功能抗体偶联的卷曲螺旋蛋白纳米颗粒用于选择性细胞靶向。

Multifunctional antibody-conjugated coiled-coil protein nanoparticles for selective cell targeting.

机构信息

Institut de Biotecnologia i de Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain.

出版信息

Acta Biomater. 2021 Sep 1;131:472-482. doi: 10.1016/j.actbio.2021.06.040. Epub 2021 Jun 27.

Abstract

Nanostructures decorated with antibodies (Abs) are applied in bioimaging and therapeutics. However, most covalent conjugation strategies affect Abs functionality. In this study, we aimed to create protein-based nanoparticles to which intact Abs can be attached through tight, specific, and noncovalent interactions. Initially considered waste products, bacterial inclusion bodies (IBs) have been used in biotechnology and biomedicine. However, the amyloid-like nature of IBs limits their functionality and raises safety concerns. To bypass these obstacles, we have recently developed highly functional α-helix-rich IBs exploiting the natural self-assembly capacity of coiled-coil domains. We used this approach to create spherical, submicrometric, biocompatible and fluorescent protein nanoparticles capable of capturing Abs with high affinity. We showed that these IBs can be exploited for Ab-directed cell targeting. Simultaneous decoration of the nanoparticles with two different Abs in a controllable ratio enabled the construction of a bispecific antibody mimic that redirected T lymphocytes specifically to cancer cells. Overall, we describe an easy and cost-effective strategy to produce multivalent, traceable protein nanostructures with the potential to be used for biomedical applications. STATEMENT OF SIGNIFICANCE: Functional inclusion bodies (IBs) are promising platforms for biomedical and biotechnological applications. These nanoparticles are usually sustained by amyloid-like interactions, which imposes some limitations on their use. In this work, we exploit the natural coiled-coil self-assembly properties to create highly functional, nonamyloid, and fluorescent IBs capable of capturing antibodies. These protein-based nanoparticles are successfully used to specifically and simultaneously target two unrelated cell types and bring them close together, becoming a technology with potential application in bioimaging and immunotherapy.

摘要

纳米结构通过抗体(Abs)进行修饰,应用于生物成像和治疗。然而,大多数共价偶联策略会影响 Abs 的功能。在这项研究中,我们旨在创建基于蛋白质的纳米颗粒,完整的 Abs 可以通过紧密、特异和非共价相互作用连接到这些纳米颗粒上。最初被认为是废物的细菌包涵体(IBs)已被用于生物技术和生物医学。然而,IBs 的类淀粉样性质限制了它们的功能,并引发了安全问题。为了克服这些障碍,我们最近利用卷曲螺旋结构域的天然自组装能力,开发了具有高度功能性的富含α-螺旋的 IBs。我们使用这种方法创建了具有球形、亚微米、生物相容性和荧光的蛋白质纳米颗粒,能够高亲和力捕获 Abs。我们表明,这些 IBs 可用于 Abs 导向的细胞靶向。通过控制纳米粒子表面同时修饰两种不同的 Abs 的比例,可以构建双特异性抗体模拟物,该模拟物将 T 淋巴细胞特异性重新导向癌细胞。总的来说,我们描述了一种简单且具有成本效益的策略,可用于生产具有潜在生物医学应用的多价、可追踪的蛋白质纳米结构。意义声明:功能性包涵体(IBs)是生物医学和生物技术应用的有前途的平台。这些纳米颗粒通常由类淀粉样相互作用维持,这对其应用有一些限制。在这项工作中,我们利用天然的卷曲螺旋自组装特性来创建高度功能性、非淀粉样和荧光 IBs,这些 IBs 能够捕获抗体。这些基于蛋白质的纳米颗粒成功地用于特异且同时靶向两种不相关的细胞类型,并使它们紧密靠近,成为一种在生物成像和免疫治疗中有潜在应用的技术。

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