4.7 Article

Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 14, Issue 4, Pages 7341-7355

Publisher

MDPI
DOI: 10.3390/ijms14047341

Keywords

chemotherapy; iron oxide nanoparticles; mitoxantrone; magnetic drug targeting; immune system; leukocytes

Funding

  1. DFG [AL 552/3-3]
  2. BMBF-Spitzencluster [01EX1012B]
  3. Else Kroner-Fresenius-Stiftung, Bad Homburg vor der Hohe, Germany
  4. Emerging Fields Initiative of the Friedrich-Alexander-University Erlangen-Nuremberg
  5. K&R Wucherpfennigstiftung
  6. Interdisciplinary Center of Clinical Research at the University Hospital Erlangen
  7. [SFB 643 TP B5]

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Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an external magnetic field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and SPIONMTO on cell viability in vitro and the nonspecific uptake of MTO into circulating leukocytes in vivo. MDT was compared with conventional chemotherapy. MTO uptake and the impact on cell viability were assessed by flow cytometry in a Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In vitro experiments showed a dose-dependent MTO uptake and reduction in the viability and proliferation of Jurkat cells. MTO and SPIONMTO showed similar cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in the concentrations tested. Compared with systemic administration in vivo, MDT employing SPIONMTO significantly decreased the chemotherapeutic load in circulating leukocytes. We demonstrated that MDT spares the immune system in comparison with conventional chemotherapy.

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