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Doxorubicin-Loaded Thermoresponsive Superparamagnetic Nanocarriers for Controlled Drug Delivery and Magnetic Hyperthermia Applications

Ferjaoui, Zied, Jamal Al Dine, Enaam, Kulmukhamedova, Aigul, Bezdetnaya, Lina, Soon Chang, Crosby, Schneider, Raphaël, Mutelet, Fabrice, Mertz, Damien, Begin-Colin, Sylvie, Quilès, Fabienne, Gaffet, Eric, Alem, Halima
ACS applied materials & interfaces 2019 v.11 no.34 pp. 30610-30620
absorption, ambient temperature, cancer therapy, cell viability, composite polymers, cytotoxicity, doxorubicin, fever, humans, iron oxides, magnetic properties, moieties, nanocarriers, nanoparticles, ovarian neoplasms
This study reports on the development of thermoresponsive core/shell magnetic nanoparticles (MNPs) based on an iron oxide core and a thermoresponsive copolymer shell composed of 2-(2-methoxy)ethyl methacrylate (MEO₂MA) and oligo(ethylene glycol)methacrylate (OEGMA) moieties. These smart nano-objects combine the magnetic properties of the core and the drug carrier properties of the polymeric shell. Loading the anticancer drug doxorubicin (DOX) in the thermoresponsive MNPs via supramolecular interactions provides advanced features to the delivery of DOX with spatial and temporal controls. The so coated iron oxide MNPs exhibit superparamagnetic behavior with a saturation magnetization of around 30 emu g–¹. Drug release experiments confirmed that only a small amount of DOX was released at room temperature, while almost 100% drug release was achieved after 52 h at 42 °C with Fe₃₋δO₄@P(MEO₂MA₆₀OEGMA₄₀), which grafted polymer chains displaying a low critical solution temperature of 41 °C. Moreover, the MNPs exhibit magnetic hyperthermia properties as shown by specific absorption rate measurements. Finally, the cytotoxicity of the core/shell MNPs toward human ovary cancer SKOV-3 cells was tested. The results showed that the polymer-capped MNPs exhibited almost no toxicity at concentrations up to 12 μg mL–¹, whereas when loaded with DOX, an increase in cytotoxicity and a decrease of SKOV-3 cell viability were observed. From these results, we conclude that these smart superparamagnetic nanocarriers with stealth properties are able to deliver drugs to tumor and are promising for applications in multimodal cancer therapy.