Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids.

Annkathrin Hornung,Stefan Lyer,Christoph Alexiou,Jan Zaloga,Johannes Nowak,Marina Poettler,Stefan Odenbach,Christina Janko,Harald Unterweger,Ralf Friedrich

doi:10.3390/molecules201018016

Abstract

Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO) with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO) are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.

Highlights

Nanomedicine offers fascinating opportunities for new medical treatments and diagnosis
Transmission microscopy revealed that the spheroids initially grew very fast, but reduced growth after prolonged incubation (Figure 1A)
By analyzing the amount of viable, apoptotic and necrotic cells, we were able to quantify the effect of SEONLA-bovine serum albumin (BSA)*MTO in comparison to free MTO in small solid tumor spheroids

Summary

Introduction

Nanomedicine offers fascinating opportunities for new medical treatments and diagnosis. Especially superparamagnetic iron oxide nanoparticles (SPION) have received scientific interest in tissue engineering, drug delivery, hyperthermia and magnetic resonance imaging techniques [1,2]. These particles can be used as a platform for targeted delivery of drugs to the desired region, guided by an external magnetic field, referred to as “magnetic drug targeting” (MDT) [3,4,5,6]. Therapeutic success using MDT in vivo has already been shown in the treatment of tumor-bearing rabbits employing mitoxantrone (MTO)-loaded iron oxide nanoparticles [13,14]

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Conclusion