Theranostic protein targeting ErbB2 for bioluminescence imaging and therapy for cancer.
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.
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan ; Japan Society for the Promotion of Science, Tokyo, Japan ; Institute of Translational Medicine, Nanchang University, Nanchang, China.
Xiao-Jian
XJ
Han
Ling-Fei
LF
Sun
Yuki
Y
Nishiyama
Bin
B
Feng
Hiroyuki
H
Michiue
Masaharu
M
Seno
Hideki
H
Matsui
Kazuhito
K
Tomizawa
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008024:Ligands; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D061848:Optical Imaging; D011485:Protein Binding; D055550:Protein Stability; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins