Development of bionanocapsules targeting brain tumors.
Bionanocapsules (BNCs) are hollow nanoparticles that are composed of L protein (the hepatitis B virus surface antigen) and show specific affinity for human hepatocytes. The pre-S1 peptide displayed on the surface of BNCs is the specific ligand for binding to the receptor on human hepatocytes. Therefore, BNCs are not delivered to other tissues, such as the brain. The aim of the present study was to develop a novel drug delivery system (DDS) targeting brain tumors using BNCs that selectively targeted brain tumors. Epidermal growth factor receptor (EGFR), especially a constitutively active genomic sequence deletion variant of EGFR (EGFRvIII), is overexpressed in human glioblastoma. In the present study, we replaced the pre-S1 peptide with the antibody affinity motif of protein A and made hybrid BNCs conjugated with anti-human EGFR antibody recognizing EGFRvIII. The hybrid BNCs were efficiently delivered to glioma cells but not normal glial cells. Moreover, we confirmed the specific delivery of the hybrid BNCs to brain tumors in an in vivo brain tumor model. These results suggest that this new approach using BNCs is a promising system for brain tumor-targeted drug delivery.
Tsutsui
Yumi
Y
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan.
Tomizawa
Kazuhito
K
Nagita
Mana
M
Michiue
Hiroyuki
H
Nishiki
Tei-ichi
T
Ohmori
Iori
I
Seno
Masaharu
M
Matsui
Hideki
H
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules; D051381:Rats; D017208:Rats, Wistar; D012235:Rhodamines / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D005456:Fluorescent Dyes; D053769:Nanocapsules; D012235:Rhodamines; D013205:Staphylococcal Protein A; C410723:epidermal growth factor receptor VIII; C027755:rhodamine isothiocyanate; D066246:ErbB Receptors