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Combinatorially Designed Lipid‐like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy
Author(s) -
Wang Ming,
Alberti Kyle,
Sun Shuo,
Arellano Carlos Luis,
Xu Qiaobing
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201311245
Subject(s) - saporin , rnase p , cytotoxic t cell , cytosol , intracellular , cancer cell , ribonuclease , in vitro , ribosome inactivating protein , chemistry , microbiology and biotechnology , cancer therapy , cytotoxicity , biochemistry , biology , cancer , rna , immunotoxin , enzyme , ribosome , genetics , gene
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.