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Stimuli-responsive lipid-based magnetic nanovectors increase apoptosis in glioblastoma cells through synergic intracellular hyperthermia and chemotherapy

Abstract

In this study, taking into consideration the limitations of the current treatments of glioblastoma multiforme, we fabricated a biomimetic lipid-based magnetic nanovector with good loading capacity and a sustained release profile of the encapsulated chemotherapeutic drug, temozolomide. These nanostructures demonstrated an enhanced release after exposure to an alternating magnetic field, and a complete release of the encapsulated drug after the synergic effect of low pH (4.5), increased concentration of hydrogen peroxide (50 μM), and increased temperature due to the applied magnetic field. In addition, these nanovectors presented excellent specific absorption rate values (up to 1345 W/g) considering the size of the magnetic component, rendering them suitable as potential hyperthermia agents. The presented nanovectors were progressively internalized in U-87 MG cells and in their acidic compartments (i.e., lysosomes and late endosomes) without affecting the viability of the cells, and their ability to cross the blood-brain barrier was preliminary investigated by using an in vitro brain endothelial cell-based model. When stimulated with alternating magnetic fields (20 mT, 750 KHz), the nanovectors demonstrated their ability to induce mild hyperthermia (43°C) and strong anticancer effects against U-87 MG cells (scarce survival of cells characterized by low proliferation rate and high apoptosis levels). The optimal anticancer effects resulted from the synergic combination of hyperthermia chronic stimulation with the controlled temozolomide release, highlighting therefore the potential of the proposed drug-loaded lipid magnetic nanovectors for the treatment of glioblastoma multiforme.

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Publication details

The article was received on 09 Jul 2018, accepted on 01 Oct 2018 and first published on 03 Oct 2018


Article type: Paper
DOI: 10.1039/C8NR05520C
Citation: Nanoscale, 2018, Accepted Manuscript
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    Stimuli-responsive lipid-based magnetic nanovectors increase apoptosis in glioblastoma cells through synergic intracellular hyperthermia and chemotherapy

    C. Tapeinos, A. Marino, M. Battaglini, S. Migliorin, R. Brescia, A. Scarpellini, M. Prato, F. Drago, C. de Julián Fernández and G. Ciofani, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR05520C

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