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Enhancement of target toxin neutralization effect in vivo by PEGylation of multifunctionalized lipid nanoparticles.
Koide, Hiroyuki; Suzuki, Hikaru; Ochiai, Hiroki; Egami, Hiromichi; Hamashima, Yoshitaka; Oku, Naoto; Asai, Tomohiro.
Afiliación
  • Koide H; Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. Electronic address: hkoide@u-shizuoka-ken.ac.jp.
  • Suzuki H; Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
  • Ochiai H; Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
  • Egami H; Department of Synthetic Organic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8526, Japan.
  • Hamashima Y; Department of Synthetic Organic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8526, Japan.
  • Oku N; Faculty of Pharma-Science, Teikyo University, 2-11-1 kaga, Itabashi-ku, Tokyo, 173-8605, Japan.
  • Asai T; Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Biochem Biophys Res Commun ; 555: 32-39, 2021 05 28.
Article en En | MEDLINE | ID: mdl-33812056
Protein-protein (e.g., antibody-antigen) interactions comprise multiple weak interactions. We have previously reported that lipid nanoparticles (LNPs) bind to and neutralize target toxic peptides after multifunctionalization of the LNP surface (MF-LNPs) with amino acid derivatives that induce weak interactions; however, the MF-LNPs aggregated after target capture and showed short blood circulation times. Here we optimized polyethylene glycol (PEG)-modified MF-LNPs (PEG-MF-LNPs) to inhibit the aggregation and increase the blood circulation time. Melittin was used as a target toxin, and MF-LNPs were prepared with negatively charged, hydrophobic, and neutral amino-acid-derivative-conjugated functional lipids. In this study, MF-LNPs modified with only PEG5k (PEG5k-MF-LNPs) and with both PEG5k and PEG2k (PEGmix-MF-LNPs) were prepared, where PEG5k and PEG2k represent PEG with a molecular weight of 5000 and 2000, respectively. PEGylation of the MF-LNPs did not decrease the melittin neutralization ability of nonPEGylated MF-LNPs, as tested by hemolysis assay. The PEGmix-MF-LNPs showed better blood circulation characteristics than the PEG5k-MF-LNPs. Although the nonPEGylated MF-LNPs immediately aggregated when mixed with melittin, the PEGmix-MF-LNPs did not aggregate. The PEGmix-MF-LNPs dramatically increased the survival rate of melittin-treated mice, whereas the nonPEGylated MF-LNPs increased slightly. These results provide a fundamental strategy to improve the in vivo toxin neutralization ability of MF-LNPs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Nanopartículas Multifuncionales / Meliteno / Antídotos Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Nanopartículas Multifuncionales / Meliteno / Antídotos Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos