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Engineering of Lipid Nanoparticles by the Multifunctionalization of the Surface with Amino Acid Derivatives for the Neutralization of a Target Toxic Peptide
Author(s) -
Koide Hiroyuki,
Hirano Satoshi,
Ide Takafumi,
Saito Kazuhiro,
Suzuki Hikaru,
Yasuno Go,
Hamashima Yoshitaka,
Yonezawa Sei,
Oku Naoto,
Asai Tomohiro
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202005641
Subject(s) - peptide , reagent , biochemistry , combinatorial chemistry , chemistry , amino acid , biocompatibility , peptide synthesis , organic chemistry
Abstract Protein affinity reagents (e.g., antibodies) are often used for basic research, diagnostics, separations, and disease therapy. Although a lot of “synthetic” protein affinity reagents have been developed as a cost‐effective alternative to antibodies, their low biocompatibility is a considerable problem for clinical application. Lipid nanoparticles (LNP) represent a highly biocompatible drug delivery agent. However, little has been reported that LNP itself works as a protein affinity reagent in living animals. Here, LNP is engineered for binding to and neutralizing a target toxic peptide in living animals by multifunctionalization with amino acid derivatives. Multifunctionalized LNP (MF‐LNP) is prepared using amino acid derivative‐conjugated lipids. Optimized MF‐LNP exhibits nanomolar affinity to the target toxic peptide and inhibits toxic peptide‐dependent hemolysis and cytotoxicity. In addition, MF‐LNP captures and neutralizes the toxic peptide after intravenous injection in the bloodstream; in addition, MF‐LNP does not release the toxic peptide in the accumulated organ. These results reveal the potential of using LNP as a highly biocompatible protein affinity reagent such as an antidote.