期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 11, 页码 2893-2898出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201311245
关键词
cancer therapy; lipidoids; nanoparticles; protein delivery
资金
- Tufts University
- Tufts FRAC award from Tufts University School of Medicine
- Charlton Award from Tufts University School of Medicine
- Pew Scholar for Biomedical Sciences program from Pew Charitable Trusts
- IGERT fellowship from NSF
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 ribonucleaseA (RNaseA) 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 invitro and suppresses tumor growth in a murine breast cancer model.
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