Theranostic protein targeting ErbB2 for bioluminescence imaging and therapy for cancer

Xiao-Jian Han1, Ling-Fei Sun, Yuki Nishiyama

  • 1Department 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.

Plos One
|September 27, 2013
PubMed

Insights

Researchers developed EC1-GLuc-p53C, a novel theranostic agent. This protein targets ErbB2-positive cancer cells for bioluminescence imaging and inhibits tumor growth by reactivating p53, offering a dual-action cancer treatment.

Area of Science:

  • Biotechnology
  • Molecular Oncology
  • Medical Imaging

Background:

  • Molecular-targeted cancer imaging and therapy offer improved diagnosis and reduced side effects.
  • ErbB2 overexpression is a hallmark of certain aggressive cancers.

Purpose of the Study:

  • To develop and evaluate a novel theranostic reagent for ErbB2-targeted cancer imaging and therapy.
  • To assess the efficacy of EC1-GLuc-p53C in vitro and in vivo.

Main Methods:

  • Generated a recombinant protein EC1-GLuc-p53C by fusing an ErbB2-targeting peptide (EC1), Gaussia luciferase (GLuc), and a p53-activating peptide (p53C).
  • Expressed and purified EC1-GLuc-p53C from E. coli.
  • Conducted in vitro assays to evaluate luminescent stability, cellular targeting, and antiproliferative effects.
  • Performed in vivo studies using tumor-bearing mice to assess bioluminescence imaging and therapeutic outcomes.

Main Results:

  • EC1-GLuc-p53C demonstrated stable luminescent activity and selective targeting of ErbB2-overexpressing BT474 cells.
  • Internalized EC1-GLuc-p53C reactivated p53 and significantly inhibited BT474 cell proliferation in vitro.
  • In vivo studies showed specific ErbB2-targeted bioluminescence imaging and therapeutic effects in BT474 tumors, but not in ErbB2-negative MCF7 tumors.

Conclusions:

  • EC1-GLuc-p53C is a promising theranostic reagent for ErbB2-positive cancers.
  • The developed protein enables simultaneous bioluminescence imaging and targeted cancer therapy.
  • This approach holds potential for improving cancer diagnosis and treatment outcomes.