TY - JOUR
T1 - Theranostic protein targeting erbb2 for bioluminescence imaging and therapy for cancer
AU - Han, Xiao Jian
AU - Sun, Ling Fei
AU - Nishiyama, Yuki
AU - Feng, Bin
AU - Michiue, Hiroyuki
AU - Seno, Masaharu
AU - Matsui, Hideki
AU - Tomizawa, Kazuhito
N1 - Funding Information:
Funding: This work was supported by grant-in-aid for Young Scientists (B) from the Ministry of Education, Science, Sports and Culture of Japan (No: 21790202,http://www.waseda.jp/rps/en/manual/kakenhi_honbun.html) and by Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science (No: 22.00119,http://www.jsps.go.jp/english/e-grants/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2013 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2013
Y1 - 2013
N2 - A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.
AB - A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.
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U2 - 10.1371/journal.pone.0075288
DO - 10.1371/journal.pone.0075288
M3 - Article
C2 - 24069396
AN - SCOPUS:84902229243
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 9 September
M1 - e0075288
ER -
