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, the absence of cell cytotoxicity, and efficient cell internalization represent strong additional needs. To achieve such requirements, we report on high-payload magnetofluorescent 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 magnetic resonance imaging (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 vs phosphonic acid), their structure (block- or comblike), their hydrophobicity, and their fabrication process [conventional or reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization] while keeping the central magnetofluorescent 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 (NAs) with enhanced-MRI negative contrast, characterized by a high r2/r1 ratio and a transverse relaxation r2 equal to 21 and 125 s-1 mmol-1 L, respectively, at 60 MHz clinical frequency (∼1.5 T). Thanks to their dual modality, cell internalization of the NAs in mesothelioma cancer cells could be evidenced by both 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 NAs that internalize at a slower rate with no adverse cytotoxicity. Extension to multicellular tumor cell spheroids that mimic solid tumors revealed the successful internalization of the NAs in the periphery cells, which provides efficient deep-imaging labels thanks to their induced T2∗ contrast, large emission Stokes shift, and bright dotlike signal, popping out of the strong spheroid autofluorescence.

PEGylated Anionic Magnetofluorescent Nanoassemblies : Impact of Their Interface Structure on Magnetic Resonance Imaging Contrast and Cellular Uptake / C. Linot, J. Poly, J. Boucard, D. Pouliquen, S. Nedellec, P. Hulin, N. Marec, P. Arosio, A. Lascialfari, A. Guerrini, C. Sangregorio, M. Lecouvey, L. Lartigue, C. Blanquart, E. Ishow. - In: ACS APPLIED MATERIALS & INTERFACES. - ISSN 1944-8244. - 9:16(2017), pp. 14242-14257. [10.1021/acsami.7b01737]

PEGylated Anionic Magnetofluorescent Nanoassemblies : Impact of Their Interface Structure on Magnetic Resonance Imaging Contrast and Cellular Uptake

P. Arosio;A. Lascialfari;
2017

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, the absence of cell cytotoxicity, and efficient cell internalization represent strong additional needs. To achieve such requirements, we report on high-payload magnetofluorescent 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 magnetic resonance imaging (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 vs phosphonic acid), their structure (block- or comblike), their hydrophobicity, and their fabrication process [conventional or reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization] while keeping the central magnetofluorescent 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 (NAs) with enhanced-MRI negative contrast, characterized by a high r2/r1 ratio and a transverse relaxation r2 equal to 21 and 125 s-1 mmol-1 L, respectively, at 60 MHz clinical frequency (∼1.5 T). Thanks to their dual modality, cell internalization of the NAs in mesothelioma cancer cells could be evidenced by both 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 NAs that internalize at a slower rate with no adverse cytotoxicity. Extension to multicellular tumor cell spheroids that mimic solid tumors revealed the successful internalization of the NAs in the periphery cells, which provides efficient deep-imaging labels thanks to their induced T2∗ contrast, large emission Stokes shift, and bright dotlike signal, popping out of the strong spheroid autofluorescence.
fluorescence; iron oxide nanoparticles water-soluble RAFT polymers; live cells; MRI; multimodal nanoassemblies; organic nanoparticles; spheroids; Materials Science (all)
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Settore FIS/03 - Fisica della Materia
Settore CHIM/07 - Fondamenti Chimici delle Tecnologie
Settore CHIM/02 - Chimica Fisica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/511967
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