Sugar Modification Enhances Cytotoxic Activity of PAMAM-Doxorubicin Conjugate in Glucose-Deprived MCF-7 Cells -

Krzysztof Sztandera1, Paula Działak1, Monika Marcinkowska1

  • 1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St, 90-236, Lodz, Poland.

Abstract

Insights

This study developed a glucose-modified dendrimer for targeted doxorubicin delivery to breast cancer cells. The formulation enhances drug efficacy by targeting glucose transporters (GLUTs) overexpressed on tumor cells, offering a promising platform for cancer therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Classical chemotherapy faces challenges including side effects and lack of targeted delivery.
  • Tumor cells exhibit heightened glucose metabolism, presenting a potential target for drug delivery systems.

Purpose of the Study:

  • To develop an innovative, glucose-modified polyamidoamine (PAMAM) dendrimer for targeted delivery of doxorubicin to breast cancer cells.
  • To leverage the intensified glucose metabolism of cancer cells for selective drug targeting.

Main Methods:

  • Synthesis and characterization of the glucose-modified PAMAM-doxorubicin conjugate (PAMAM-dox-glc).
  • Evaluation of drug release kinetics under varying pH conditions.
  • Assessment of glucose transporter (GLUT) family receptor expression via RT-PCR and flow cytometry.
  • Determination of conjugate cytotoxicity using MTT assay, with and without GLUT1 inhibitors.

Main Results:

  • The PAMAM-dox-glc conjugate demonstrated pH-dependent doxorubicin release.
  • Enhanced cytotoxic activity was observed in glucose-deprived medium, correlating with GLUT family receptor overexpression in cancer cells.
  • Specific GLUT1 inhibitors effectively eliminated the toxic effect of the conjugate, confirming targeted uptake.

Conclusions:

  • Glucose modification is critical for the recognition and uptake of the dendrimer by cells overexpressing GLUT receptors.
  • The GLUT1 transporter plays a significant role in the cytotoxic efficacy of the PAMAM-dox-glc conjugate.
  • PAMAM-glucose formulations represent a viable platform for targeted anticancer drug delivery to tumors with high GLUT transporter expression.

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