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Combinatorially Designed Lipid-like Nanoparticles For Intracellular Delivery Of Cytotoxic Protein For Cancer Therapy.

M. Wang, Kyle A. Alberti, Shuo Sun, Carlos Luis Arellano, Qiaobing Xu
Published 2014 · Chemistry, Medicine

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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.
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