Antibody-modified lipid nanoparticles for selective delivery of siRNA to tumors expressing membrane-anchored form of HB-EGF.
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.
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Ayaka
A
Okamoto
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Tomohiro
T
Asai
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Hiroki
H
Kato
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Hidenori
H
Ando
Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tetsuo
T
Minamino
Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Eisuke
E
Mekada
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.
Naoto
N
Oku
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D020868:Gene Silencing; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000276:immunology*; D053758:Nanoparticles; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D014709:Vero Cells
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D007140:Immunoglobulin Fab Fragments; D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering
Antibody; Breast cancer; HB-EGF; Lipid nanoparticles; siRNA delivery