Development of a bifunctional immunoliposome system for combined drug delivery and imaging in vivo.
The diverse characteristics of immunoliposomes provide advantages for utilization in drug delivery systems. In this study, we fused the antibody affinity motif of protein A (ZZ) with Gaussia luciferase (GLase). The fused protein conjugated with an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (GLase-ZZ-His-mAb) was effectively delivered into glioma cells expressing an activated EGFR mutant (EGFRvIII) and the bioluminescence was visualized in the cells. Immunoliposomes were further constructed with DSPE-PEG-MAL for covalent GLase-ZZ-His-mAb conjugation. A fluorescence dye (HPTS) encapsulated in immunoliposomes conjugated with GLase-ZZ-His-mAb was effectively delivered into EGFRvIII-expressing glioma cells. In a murine xenograft model of glioma, moreover, specific targeting of the immunoliposomes was visualized in the tumor. This new bifunctional immunoliposome system has the potential for drug delivery and imaging in vivo.
Feng
Bin
B
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tomizawa
Kazuhito
K
Michiue
Hiroyuki
H
Han
Xiao-Jian
XJ
Miyatake
Shin-ichi
S
Matsui
Hideki
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D008081:Liposomes / Q000276:immunology*; D008156:Luciferases / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D009154:Mutation / Q000235:genetics; D011721:Pyrenes / Q000378:metabolism; D015203:Reproducibility of Results; D013451:Sulfonic Acids / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C538892:8-hydroxy-1,3,6-pyrenetrisulfonic acid; D000911:Antibodies, Monoclonal; D008081:Liposomes; D011721:Pyrenes; D013451:Sulfonic Acids; D008156:Luciferases; D066246:ErbB Receptors