Doxorubicin Intracellular Remote Release from Biocompatible OEGMA-based Magnetic Nanogels Triggered by Magnetic Hyperthermia ;
ACS Appl. Mater. Interfaces, 2017, DOI : 10.1021/acsami.7b06553
Esther Cazares-Cortes, Ana Espinosa, Jean-Michel Guigner, Aude Michel, Nébéwia Griffete, Claire Wilhelm, and Christine Ménager
Contact PHENIX : christine.menager@upmc.fr
Abstract
Hybrid nanogels, composed of thermoresponsive polymers and superparamagnetic nanoparticles (MNPs) are attractive nanocarriers for biomedical applications, being able – as polymer matrix – to uptake and release high quantities of chemotherapeutic agents and – as magnetic nanoparticles – to heat when exposed to an alternative magnetic field (AMF), better known as magnetic hyperthermia. Herein, biocompatible, pH-, magnetic- and thermo-responsive nanogels, based on oligo (ethylene glycol) methacrylate monomers (OEGMAs) and methacrylic acid co-monomer (MAA) were prepared by conventional precipitation radical co-polymerization in water, post-assembled by complexation with iron oxide magnetic nanoparticles (MNPs) of maghemite (γ-Fe2O3) and loaded with an anticancer drug (doxorubicin – DOX), for remotely controlled drug release by “hot-spot”, as an athermal magnetic hyperthermia strategy against cancer.
These nanogels, noted MagNanoGels, with a hydrodynamic diameter from 328 to 460 nm, as a function of MNPs content, have a swelling-deswelling behavior at their volume phase temperature transition (VPTT) around 47 °C in a physiological medium (pH 7.5), which is above the human body temperature (37 °C). Applying an alternative magnetic field increases twice the release of DOX, while no macroscopic heating was recorded. This enhanced drug release is due to a shrinking of the polymer network by local heating, as illustrated by the MagNanoGels size decrease under AMF. In cancer cells, not only the DOX-MagNanoGels internalize DOX more efficiently than free DOX, but also DOX intracellular release can be remotely triggered under AMF, in athermal conditions, thus enhancing DOX cytotoxicity.
