Toxicity of Mitoxantrone-loaded Superparamagnetic Iron Oxide Nanoparticles in a HT-29 Tumour Spheroid Model.
OBJECTIVE
Cancer research is commonly carried out in two-dimensional (2D) cell cultures, which poorly reflect in vivo settings where the growing tumours are exposed to mechanical forces and biochemical gradients. In this study we established a HF-29 colon carcinoma tumor spheroid model to investigate the effect of free mitoxantrone (MTO) and its nanoparticle-bound form (SPION(MTO)) under 3D cell culture conditions.


METHODS
Tumour spheroids were generated by seeding HT-29 colon carcinoma cells on agarose-coated cell culture wells. Growth of the spheroids was monitored daily by transmission microscopy upon treatment with free MTO, SPION(MTO) or unloaded SPION.


CONCLUSIONS
Unloaded SPION did not affect the spheroid size compared to untreated controls, while both free MTO and SPION(MTO) inhibited growth of the spheroids in a dose- and time-dependent manner. In comparison to free MTO, the effect of SPION(MTO) on spheroid growth was slightly delayed. Further analyses are necessary to investigate if MTO infiltrates spheroids in its nanoparticle-bound form or whether it is released from SPION before infiltration.
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Annkathrin
A
Hornung
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Marina
M
Poettler
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Ralf P
RP
Friedrich
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Bianca
B
Weigel
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany Department of Otorhinolaryngology, Section of Phoniatrics & Pediatric Audiology, Head & Neck Surgery, University Hospital Erlangen, Erlangen, Germany.
Stephan
S
Duerr
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Jan
J
Zaloga
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Iwona
I
Cicha
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany.
Christoph
C
Alexiou
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, University Hospital Erlangen, Erlangen, Germany christina.janko@uk-erlangen.de.
Christina
C
Janko
D000970:Antineoplastic Agents / Q000633:toxicity*; D005290:Ferric Compounds / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D008942:Mitoxantrone / Q000633:toxicity*; D018874:Spheroids, Cellular
D000970:Antineoplastic Agents; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D008942:Mitoxantrone
Tumour spheroids; magnetic drug targeting; mitoxantrone; nanotoxicology