Antibody-modified lipid nanoparticles for selective delivery of siRNA to tumors expressing membrane-anchored form of HB-EGF

Ayaka Okamoto; Tomohiro Asai; Hiroki Kato; Hidenori Ando; Tetsuo Minamino; Eisuke Mekada; Naoto Oku

doi:10.1016/j.bbrc.2014.05.043

Antibody-modified lipid nanoparticles for selective delivery of siRNA to tumors expressing membrane-anchored form of HB-EGF

Biochem Biophys Res Commun. 2014 Jul 11;449(4):460-5. doi: 10.1016/j.bbrc.2014.05.043. Epub 2014 May 20.

Authors

Ayaka Okamoto¹, Tomohiro Asai¹, Hiroki Kato¹, Hidenori Ando¹, Tetsuo Minamino², Eisuke Mekada³, Naoto Oku⁴

Affiliations

¹ Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
² Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
³ Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁴ Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: oku@u-shizuoka-ken.ac.jp.

PMID: 24853808
DOI: 10.1016/j.bbrc.2014.05.043

Abstract

An Fab' antibody against heparin-binding epidermal growth factor-like growth factor (HB-EGF) was applied to achieve advanced tumor-targeted delivery of siRNA. Lipid nanoparticles (LNP) encapsulating siRNA (LNP-siRNA) were prepared, pegylated, and surface modified with Fab' fragments of anti-HB-EGF antibody (αHB-EGF LNP-siRNA). αHB-EGF LNP-siRNA showed high-binding affinity to recombinant human HB-EGF in a Biacore assay. In addition, αHB-EGF LNP-siRNA selectively associated with cells expressing HB-EGF in vitro. Confocal microscopic images showed that siRNA formulated in αHB-EGF LNP-siRNA was efficiently internalized into MDA-MB-231 human breast cancer cells, on which HB-EGF is highly expressed. In addition, siRNA encapsulated in αHB-EGF LNP induced obvious suppression of both target mRNA and protein levels in MDA-MB-231 cells. These results indicate that αHB-EGF LNP have excellent potential to deliver siRNA to target cancer cells, resulting in effective gene silencing.

Keywords: Antibody; Breast cancer; HB-EGF; Lipid nanoparticles; siRNA delivery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism
Chlorocebus aethiops
Female
Gene Silencing
Heparin-binding EGF-like Growth Factor
Humans
Immunoglobulin Fab Fragments / administration & dosage*
Intercellular Signaling Peptides and Proteins / biosynthesis
Intercellular Signaling Peptides and Proteins / immunology*
Nanoparticles
RNA, Small Interfering / administration & dosage*
Tumor Cells, Cultured
Vero Cells

Substances

HBEGF protein, human
Heparin-binding EGF-like Growth Factor
Immunoglobulin Fab Fragments
Intercellular Signaling Peptides and Proteins
RNA, Small Interfering