Abstract

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.

Highlights

  • Together with surgery and radiotherapy, chemotherapy is still a mainstay of cancer treatment today.Its main disadvantage lies in the severe systemic adverse effects inherent in this mode of therapy

  • Measurements were performed at a medium flow rate setting; (C) Analysis of MTO loading on superparamagnetic iron oxide nanoparticles (SPION) by high performance liquid chromatography (HPLC) and flow cytometry. 10 μL SPIONMTO were diluted in 500 μL

  • Magnetic drug targeting (MDT) reduces the chemotherapeutic burden of circulating leukocytes

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Summary

Introduction

Together with surgery and radiotherapy, chemotherapy is still a mainstay of cancer treatment today. Magnetic drug targeting (MDT), a new and innovative approach, has been developed to concentrate anticancer drugs in the tumor and reduce leakage into healthy tissues and cells. More and more attention is being paid to the immunological aspects of cancer therapy: antibodies [10], vaccines [11], and the induction of anti-tumor immunity during radiotherapy and chemotherapy [12]. This pilot study aimed to quantify MTO in peripheral blood leukocytes (PBL) using its inherent fluorescent properties, since. The solution is injected into the vascular supply of the tumor and accumulated at the intended site by means of an external magnetic field

Analysis of SPION by Flow Cytometry
Uptake of MTO and SPIONMTO by Jurkat Cells
MDT Reduced the MTO Load of Circulating Leukocytes in Vivo
Tumor Model
Chemotherapeutic Agent
Nanoparticles
Mode of Administration
Cells and Culture Conditions
Measurement of Cellular Morphology
Flow Cytometry
Conclusions
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