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Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
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Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells

Published on: May 9, 2025

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Design and biological activity of epidermal growth factor receptor-targeted peptide doxorubicin conjugate

Mingliang Fan1, Danbo Yang1, Xiaofei Liang1

  • 1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 18, 2015
PubMed

Insights

This study introduces GE11-DOX, a targeted anticancer drug conjugate. GE11-DOX shows enhanced delivery to EGFR-overexpressing tumors, reducing side effects of doxorubicin (DOX).

Area of Science:

  • Oncology
  • Drug Delivery
  • Bioconjugation

Background:

  • Nonspecific toxicity of doxorubicin (DOX) limits its clinical use.
  • Targeted drug delivery aims to reduce side effects and improve efficacy.
  • Epidermal growth factor receptor (EGFR) is overexpressed in various cancers.

Purpose of the Study:

  • To develop and evaluate a novel GE11-DOX conjugate for targeted cancer therapy.
  • To investigate the cellular uptake and cytotoxicity of GE11-DOX in cancer cell models.
  • To confirm the role of the EGFR pathway in GE11-DOX delivery.

Main Methods:

  • Synthesis of GE11-DOX conjugate via a disulfide bond cleavable by reduced glutathione (GSH).
  • In vitro assessment of intracellular delivery and cytotoxicity in high (SMMC-7721) and low (MCF-7) EGFR-expressing cancer cells.
  • Evaluation of EGFR pathway involvement using anti-EGFR monoclonal antibody pretreatment.

Main Results:

  • GE11-DOX exhibited significantly higher accumulation in EGFR-overexpressing SMMC-7721 cells compared to MCF-7 cells.
  • Cellular uptake of free DOX was comparable in both cell lines, indicating targeted delivery of the conjugate.
  • Inhibition of EGFR signaling reduced GE11-DOX intracellular accumulation, confirming EGFR-mediated transport.

Conclusions:

  • GE11-DOX conjugate demonstrates targeted intracellular delivery via the EGFR pathway.
  • The GE11-DOX conjugate shows potential as a therapeutic agent for EGFR-overexpressing tumors.
  • This targeted approach may mitigate the systemic toxicity associated with conventional doxorubicin therapy.
Keywords:
Epidermal growth factor receptorPeptide drug conjugateTargeted drug delivery

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