<p>Tuning the surface coating of IONs toward efficient sonochemical tethering and sustained liberation of topoisomerase II poisons</p>
Authors: Zbynek Heger
Vladislav Strmiska
Zuzana Skubalova
Hana Michalkova
Pavel Svec
Jiri Kudr
Barbora Tesarova
Vojtech Adam
Lukas Richtera
Ondrej Zitka
Journal: International Journal of Nanomedicine (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: doxorubicin; ellipticine; iron oxide; nanoparticles; release kinetics.
Affiliations: Department of Chemistry and Biochemistry, Mendel University in Brno, Brno CZ-613 00, Czech Republic., Smart Nanodevices Research Group, Central European Institute of Technology, Brno University of Technology, Brno CZ-621 00, Czech Republic.

Abstract:  Background: Iron oxide nanoparticles (IONs) have been increasingly utilized in a wide spectrum of biomedical applications. Surface coatings of IONs can bestow a number of exceptional properties, including enhanced stability of IONs, increased loading of drugs or their controlled release. Methods: Using two-step sonochemical protocol, IONs were surface-coated with polyoxyethylene stearate, polyvinylpyrrolidone or chitosan for a loading of two distinct topo II poisons (doxorubicin and ellipticine). The cytotoxic behavior was tested in vitro against breast cancer (MDA-MB-231) and healthy epithelial cells (HEK-293 and HBL-100). In addition, biocompatibility studies (hemotoxicity, protein corona formation, binding of third complement component) were performed. Results: Notably, despite surface-coated IONs exhibited only negligible cytotoxicity, upon tethering with topo II poisons, synergistic or additional enhancement of cytotoxicity was found in MDA-MB-231 cells. Pronounced anti-migratory activity, DNA fragmentation, decrease in expression of procaspase-3 and enhancement of p53 expression were further identified upon exposure to surface-coated IONs with tethered doxorubicin and ellipticine. Moreover, surface-coated IONs nanoformulations of topo II poisons exhibited exceptional stability in human plasma with no protein corona and complement 3 binding, and only a mild induction of hemolysis in human red blood cells. Conclusion: The results imply a high potential of an efficient ultrasound-mediated surface functionalization of IONs as delivery vehicles to improve therapeutic efficiency of topo II poisons. 

Retracted: No

PubPeer comments:
 Unless I am severely mistaken, Figure 1D appears to be a collage of repeated images. See matching colors, including repeated features to help identify. *** Image enhanced ![file] *** Original ![file] , 
 Yes it is an error. Thank you for pointing out! , 
 Dear Dr. Tesarova et al., I agree with the findings of Actinopolyspora Biskrensis. But I do no quite understand your answer that it was an error. How could not just one set of panels, but four set have been accidentally have been duplicated? Where the photos not labeled clearly? Four sets of duplications is a lot in a single figure, and it casts serious doubts about the record keeping in a lab. Also, did you already submit a corrigendum to the journal? I cannot seem to find a correction, but I might be mistaken. Thank you, Elisabeth Bik , 
 Now that I am here, there appears to also be a set of panels that look similar to each other in Figure 6A. I have marked these panels here with blue boxes. Could the authors please check this figures as well? ![file] , 
 The authors have advised due to an error at the time of figure assembly, Figure 1D on page 7614 and Figure 6A on page 7621 is incorrect. The correct figures are shown below. ![file] ![file] ,