TY - JOUR
T1 - Development of bionanocapsules targeting brain tumors
AU - Tsutsui, Yumi
AU - Tomizawa, Kazuhito
AU - Nagita, Mana
AU - Michiue, Hiroyuki
AU - Nishiki, Tei-ichi
AU - Ohmori, Iori
AU - Seno, Masaharu
AU - Matsui, Hideki
N1 - Funding Information:
This work was supported by the Research Program on Development of Innovative Technology from the Japan Science and Technology Agency (JST), by a grant from the New Energy and Industrial Technology Development Organization (NEDO), by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and by a Grant-in Aid for Scientific Research from the Ministry of Health, Labour and Welfare of Japan.
PY - 2007/9/26
Y1 - 2007/9/26
N2 - 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.
AB - 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.
KW - Brain tumor
KW - Drug delivery system (DDS)
KW - Gene therapy
KW - Hepatitis virus B (HBV)
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U2 - 10.1016/j.jconrel.2007.06.019
DO - 10.1016/j.jconrel.2007.06.019
M3 - Article
C2 - 17692421
AN - SCOPUS:34548402938
SN - 0168-3659
VL - 122
SP - 159
EP - 164
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -
