Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA).
Angew Chem Int Ed Engl. 2014 Mar 10;53(11):2893-8. doi: 10.1002/anie.201311245. Epub 2014 Feb 12.
An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model.
高效且安全地将活性蛋白递送至靶细胞的细胞质中，对于推进基于蛋白质的治疗方法至关重要。本研究通过组合设计阳离子类脂材料（称为“脂质体”），并结合可逆化学蛋白质工程方法，创建了一种新型蛋白质递药平台。使用核糖核酸酶 A（RNase A）和丝裂原作为两种代表性的细胞毒性蛋白，组合脂质体有效地将蛋白递送至癌细胞内，并抑制细胞增殖。对结构-功能关系的研究表明，脂质体与蛋白之间的静电和疏水相互作用在蛋白-脂质体纳米复合物的形成和细胞内递送上起着至关重要的作用。代表性的脂质体（EC16-1）蛋白纳米粒制剂在体外抑制细胞增殖，并在小鼠乳腺癌模型中抑制肿瘤生长。
