Mitoxantrone and Mitoxantrone-Loaded Iron Oxide Nanoparticles Induce Cell Death in Human Pancreatic Ductal Adenocarcinoma Cell Spheroids

Dinter J, Friedrich RP, Yang H, Pilarsky C, Mangge H, Pöttler M, Janko C, Alexiou C, Lyer S (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Materials MDPI

Book Volume: 16

Article Number: 2906

Journal Issue: 7

DOI: 10.3390/ma16072906

Abstract

Pancreatic ductal adenocarcinoma is a hard-to-treat, deadly malignancy. Traditional treatments, such as surgery, radiation and chemotherapy, unfortunately are still not able to significantly improve long-term survival. Three-dimensional (3D) cell cultures might be a platform to study new drug types in a highly reproducible, resource-saving model within a relevant pathophysiological cellular microenvironment. We used a 3D culture of human pancreatic ductal adenocarcinoma cell lines to investigate a potential new treatment approach using superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for mitoxantrone (MTO), a chemotherapeutic agent. We established a PaCa DD183 cell line and generated PANC-1^{SMAD4 (−/−)} cells by using the CRISPR-Cas9 system, differing in a prognostically relevant mutation in the TGF-β pathway. Afterwards, we formed spheroids using PaCa DD183, PANC-1 and PANC-1^{SMAD4 (−/−)} cells, and analyzed the uptake and cytotoxic effect of free MTO and MTO-loaded SPIONs by microscopy and flow cytometry. MTO and SPION–MTO-induced cell death in all tumor spheroids in a dose-dependent manner. Interestingly, spheroids with a SMAD4 mutation showed an increased uptake of MTO and SPION–MTO, while at the same time being more resistant to the cytotoxic effects of the chemotherapeutic agents. MTO-loaded SPIONs, with their ability for magnetic drug targeting, could be a future approach for treating pancreatic ductal adenocarcinomas.

Authors with CRIS profile

Jonas Dinter Professur für Nanomedizin Hai Yang Department of Surgery Christian Pilarsky Professur für Chirurgische Forschung Christina Janko Department of Otorhinolaryngology – Head and Neck Surgery Christoph Alexiou Professur für Nanomedizin Stefan Lyer Department of Otorhinolaryngology – Head and Neck Surgery

Involved external institutions

Medizinische Universität Graz

Austria (AT)

How to cite

APA:

Dinter, J., Friedrich, R.P., Yang, H., Pilarsky, C., Mangge, H., Pöttler, M.,... Lyer, S. (2023). Mitoxantrone and Mitoxantrone-Loaded Iron Oxide Nanoparticles Induce Cell Death in Human Pancreatic Ductal Adenocarcinoma Cell Spheroids. Materials, 16(7). https://doi.org/10.3390/ma16072906

MLA:

Dinter, Jonas, et al. "Mitoxantrone and Mitoxantrone-Loaded Iron Oxide Nanoparticles Induce Cell Death in Human Pancreatic Ductal Adenocarcinoma Cell Spheroids." Materials 16.7 (2023).

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