Tuning the surface coating of IONs toward efficient sonochemical tethering and sustained liberation of topoisomerase II poisons

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.

Keywords

doxorubicin, ellipticine, iron oxide, nanoparticles, release kinetics

Citation

International Journal of Nanomedicine. 2019, vol. 14, issue 1, p. 7609-7624.
https://www.dovepress.com/tuning-the-surface-coating-of-ions-toward-efficient-sonochemical-tethe-peer-reviewed-article-IJN

Document type

Peer-reviewed

Document version

Published version

Language of document

en

Document licence

Creative Commons Attribution-NonCommercial 3.0 Unported
http://creativecommons.org/licenses/by-nc/3.0/