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Doxorubicin Intracellular Remote Release from Biocompatible Oligo(ethylene glycol) Methyl Ether Methacrylate-Based Magnetic Nanogels Triggered by Magnetic Hyperthermia

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 2 (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 (-Fe 2 O 3) 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.
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https://hal.sorbonne-universite.fr/hal-01586118
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Submitted on : Tuesday, September 12, 2017 - 2:45:07 PM
Last modification on : Wednesday, December 9, 2020 - 3:12:36 PM
Long-term archiving on: : Wednesday, December 13, 2017 - 2:04:30 PM

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Esther Cazares-Cortes, Ana Espinosa, Jean-Michel Guigner, Aude Michel, Nébéwia Griffete, et al.. Doxorubicin Intracellular Remote Release from Biocompatible Oligo(ethylene glycol) Methyl Ether Methacrylate-Based Magnetic Nanogels Triggered by Magnetic Hyperthermia. ACS Applied Materials & Interfaces, Washington, D.C. : American Chemical Society, 2017, 9 (31), pp.25775-25788. ⟨10.1021/acsami.7b06553⟩. ⟨hal-01586118⟩

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