Chang Jenny R, Song Eun-Ho, Nakatani-Webster Eri, Monkkonen Lucas, Ratner Daniel M, Catalano Carlos E
Department of Medicinal Chemistry, School of Pharmacy, University of Washington H-172, Health Sciences Building, Box 357610, Seattle, Washington 98195-7610, United States.
Biomacromolecules. 2014 Dec 8;15(12):4410-9. doi: 10.1021/bm5011646. Epub 2014 Nov 20.
Nanoparticle technologies provide a powerful tool for the development of reagents for use in both therapeutic and diagnostic, or "theragnostic" biomedical applications. Two broad classes of particles are under development, viral and synthetic systems, each with their respective strengths and limitations. Here we adapt the phage lambda system to construct modular "designer" nanoparticles that blend these two approaches. We have constructed a variety of modified "decoration" proteins that allow site-specific modification of the shell with both protein and nonproteinaceous ligands including small molecules, carbohydrates, and synthetic display ligands. We show that the chimeric proteins can be used to simultaneously decorate the shell in a tunable surface density to afford particles that are physically homogeneous and that can be manufactured to display a variety of ligands in a defined composition. These designer nanoparticles set the stage for development of lambda as a theragnostic nanoparticle system.
纳米颗粒技术为开发用于治疗和诊断或“治疗诊断一体化”生物医学应用的试剂提供了强大工具。目前正在开发两大类颗粒,即病毒系统和合成系统,它们各有优缺点。在此,我们采用噬菌体λ系统构建模块化“定制”纳米颗粒,将这两种方法结合起来。我们构建了多种经过修饰的“装饰”蛋白,这些蛋白能够对衣壳进行位点特异性修饰,修饰物包括蛋白质和非蛋白质配体,如小分子、碳水化合物和合成展示配体。我们证明,这些嵌合蛋白可用于以可调的表面密度同时装饰衣壳,从而获得物理性质均一的颗粒,并且可以将其制备成以确定组成展示多种配体的颗粒。这些定制纳米颗粒为将λ噬菌体开发成一种治疗诊断一体化纳米颗粒系统奠定了基础。