title: Combinatorially designed lipid-like nanoparticles for intracellular delivery of cytotoxic protein for cancer therapy.
abstract: 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.
authors: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA (USA).
authors: Ming
authors: M
authors: Wang
authors: Kyle
authors: K
authors: Alberti
authors: Shuo
authors: S
authors: Sun
authors: Carlos Luis
authors: CL
authors: Arellano
authors: Qiaobing
authors: Q
authors: Xu
mesh_terms: D000156:Aconitic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D000473:Alkanes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D054789:Ribosome Inactivating Proteins, Type 1 / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D000076985:Saporins
chemical_list: D000473:Alkanes; D000588:Amines; D000970:Antineoplastic Agents; D008055:Lipids; D054789:Ribosome Inactivating Proteins, Type 1; C064873:aconitic anhydride; C010720:1,2-epoxyhexadecane; D000156:Aconitic Acid; D012259:Ribonuclease, Pancreatic; D000076985:Saporins
keywords: cancer therapy; lipidoids; nanoparticles; protein delivery