Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität Mainz , Staudingerweg 5, 55128 Mainz, Germany.
J Am Chem Soc. 2016 Nov 16;138(45):14820-14823. doi: 10.1021/jacs.6b06243. Epub 2016 Aug 17.
Nature's biomaterials such as peptides and proteins represent a valuable source of highly defined macromolecules. Herein we developed a nanoparticle drug delivery system based on the assembly of surface-modified proteins that can be transferred into organic solvents and represent the structural material of the carrier system. The particles are prepared by an oil-in-water nanoemulsion technique without the need of additional denaturation or cross-linking steps for stabilization. We achieve the necessary lipophilic solubility switch of the protein material by high surface PEGylation under conservation of the native three-dimensional protein structure. This study focuses on lysozyme as model enzyme for the preparation of empty and doxorubicin-loaded nanoparticles with an average diameter of 100 nm. The particles are stable in physiological buffers and only release their therapeutic payload into cancer cells after a time-dependent cellular uptake. We also transferred this approach to various proteins, exemplifying the universal applicability of our new preparation method for protein-based nanoparticles.
自然界中的生物材料，如肽和蛋白质，是高度定义的大分子的宝贵来源。在此，我们开发了一种基于表面修饰蛋白质组装的纳米颗粒药物递送系统，该系统可转移到有机溶剂中，并作为载体系统的结构材料。这些颗粒是通过油包水纳米乳液技术制备的，无需额外的变性或交联步骤来稳定。我们通过在保持天然三维蛋白质结构的情况下进行高表面 PEG 化，实现了蛋白质材料必需的亲脂性溶解度转换。本研究以溶菌酶为模型酶，制备了载有空和阿霉素的纳米颗粒，平均粒径为 100nm。这些颗粒在生理缓冲液中稳定，只有在细胞摄取后经过时间依赖性释放才能将治疗有效载荷递送到癌细胞中。我们还将这种方法转移到各种蛋白质上，证明了我们新的基于蛋白质的纳米颗粒制备方法的通用性。
