PEGylated Anionic Magneto-Fluorescent Nanoassemblies: Impact of their Interface Structure on MRI Contrast and Cellular Uptake

Abstract : Controlling the interactions of functional nanostructures with water and biological media represents high challenges in the field of bioimaging applications. Large contrast at low doses, high colloidal stability in physiological conditions, absence of cell cytotoxicity and efficient cell internalization represent strong additional needs. To achieve such requirements, we report on high payload magneto-fluorescent architectures, made of a shell of superparamagnetic iron oxide nanoparticles tightly anchored around fluorescent organic nanoparticles. Their external coating is simply modulated using anionic polyelectrolytes in a final step to provide efficient MRI and fluorescence imaging of live cells. Various structures of pegylated polyelectrolytes have been synthesized and investigated, differing from their iron oxide complexing units (carboxylic versus phosphonic acid), their structure (block or comb-like), their hydrophobicity and their fabrication process (conventional or RAFT-controlled radical polymerization) while keeping the central magneto-fluorescent platforms the same. Combined photophysical, magnetic, NMRD and structural investigations proved the superiority of RAFT polymer coatings containing carboxylate units and a hydrophobic tail to impart the magnetic nanoassemblies with enhanced-MRI negative contrast, characterized by a high r2/r1 ratio and transverse relaxation r2 equal to 21 and 125 s-1mmol-1L respectively at 60 MHz clinical frequency (~1.5 T). Thanks to their dual modality, cell internalization of the nanoassemblies in mesothelioma cancer cells could be evidenced both by confocal fluorescence microscopy and magnetophoresis. A 72 h follow-up showed efficient uptake after 24 h with no notable cell mortality. These studies again pointed out the distinct behavior of RAFT polyelectrolyte-coated bimodal nanoassemblies that internalize at a slower rate with no adverse cytotoxicity. Extension to multicellular tumor cell spheroids that mimic solid tumors revealed successful internalization of the nanoassemblies in the periphery cells, which provides efficient deep-imaging labels thanks to their induced T2* contrast, large emission Stokes shift and bright dot-like signal, popping out of the strong spheroid autofluorescence.
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ACS Applied Materials & Interfaces, Washington, D.C. : American Chemical Society, 2017, 9 (16), pp.14242-14257. 〈10.1021/acsami.7b01737〉
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Camille Linot, Julien Poly, Joanna Boucard, Daniel Pouliquen, Steven Nedellec, et al.. PEGylated Anionic Magneto-Fluorescent Nanoassemblies: Impact of their Interface Structure on MRI Contrast and Cellular Uptake. ACS Applied Materials & Interfaces, Washington, D.C. : American Chemical Society, 2017, 9 (16), pp.14242-14257. 〈10.1021/acsami.7b01737〉. 〈inserm-01522631〉

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