ABSTRACT
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.
Subject(s)
Doxorubicin , Drug Carriers , Hot Temperature , Hyperthermia, Induced , Magnetite Nanoparticles , Neoplasms , Cell Line, Tumor , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Humans , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/therapyABSTRACT
The unique physical properties of the superparamagnetic nanoparticles (SPIONs) have made them candidates of choice in nanomedicine especially for diagnostic imaging, therapeutic applications and drug delivery based systems. In this study, superparamagnetic Fe3O4 NPs were synthesized and functionalized with a biocompatible thermoresponsive copolymer to obtain temperature responsive core/shell NPs. The ultimate goal of this work is to build a drug delivery system able to release anticancer drugs in the physiological temperatures range. The core/shell NPs were first synthesized and their chemical, physical, magnetic and thermo-responsive properties where fully characterized in a second step. The lower critical solution temperature (LCST) of the core/shell NPs was tuned in physiological media in order to release the cancer drug at a controlled temperature slightly above the body temperature to avoid any premature release of the drug. The core/shell NPs exhibiting the targeted LCST were then loaded with Doxurubicin (DOX) and the drug release properties were then studied with the temperature. Moreover the cytotoxicity tests have shown that the core/shell NPs had a very limited cytotoxicity up to concentration of 25µg/mL. This investigation showed that the significant release occurred at the targeted temperature in the physiological media making those nano-systems very promising for further use in drug delivery platform.
