The dysregulation of microRNAs (miRNAs) has been implicated in a variety of pathologies, such as inflammatory and autoimmune diseases, neurological disorders, as well as several types of cancer. Anti-miRNA platforms highly effective in in-vitro cell assays have been reported, but translation to the clinic is hampered by poor in-vivo stability of nucleic acids and ineffective uptake of nucleic acids by target cells. This study aims to overcome these obstacles by designing, producing and testing in-vivo new miRNA targeting materials constituted by Peptide Nucleic Acids (PNAs, synthetic mimics of natural DNA and RNA) [1]. Indeed, PNAs conjugate the effectiveness of the natural nucleic acids targeting with chemical/thermal stability and resistance to enzymatic biodegradation. In order to follow the fate of PNA and improve its solubility and permeability to cells, PNA has been linked to superparamagnetic iron oxide nanoparticles (SPIONs), affording new nanocomposites which will be exploited both as contrast agents for magnetic resonance imaging (MRI) and as sources of local overheating through the application of an alternating magnetic filed (Magnetic Fluid Hyperthermia, MHF). SPIONs have been prepared by a slightly modified thermal decomposition method [2] in order to optimize in particular the hyperthermia effectiveness [3]. Then, the oleate layer has been exchanged with dimercaptosuccinic acid (DMSA) which is a bifunctional small molecule, able to efficiently substitute the oleate capping agent [4]. This way both COOH and SH groups can be exploited to link PNA to the NP surface. In this work the synthesis of the magnetic NPs, their characterization and their functionalization with PNA are presented. References [1] P. E. Nielsen, M. Egholm, R. H. Berg, O. Buchardt, Science, 254 (1991) 1497. [2] P. Calcagnile, D. Fragouli, I. S. Bayer, G. C. Anyfantis, L. Martiradonna, P. D. Cozzoli, R. Cingolani, A. Athanassiou, ACS Nano, 6 (2012) 5413. [3] G. F. Goya, V. Grazu, M. R. Ibarra, Curr. Nanosci., 4 (2008) 1. [4] A. Ruiz, P. C. Morais, R. Bentes de Azevedo, Z. G. M. Lacava, A. Villanueva, M. del Puerto Morales, J Nanopart. Res., 16 (2014) 2589.

Iron Oxide-PNA nanoparticles for miRNA targeting / A. Maggioni, D. Dova, A. Guerrini, C. Carrara, P.R. Thakare, M. Galli, C. Sangregorio, S. Cauteruccio, M. Panigati, E. Licandro, R. Pennati, F. Orsini, P. Arosio, A. Lascialfari. ((Intervento presentato al convegno Trends in Nanotechnology International Conference tenutosi a Toulouse nel 2015.

Iron Oxide-PNA nanoparticles for miRNA targeting

D. Dova
Secondo
;
C. Carrara;P.R. Thakare;M. Galli;S. Cauteruccio;M. Panigati;E. Licandro;R. Pennati;F. Orsini;P. Arosio
Penultimo
;
A. Lascialfari
Ultimo
2015-09-07

Abstract

The dysregulation of microRNAs (miRNAs) has been implicated in a variety of pathologies, such as inflammatory and autoimmune diseases, neurological disorders, as well as several types of cancer. Anti-miRNA platforms highly effective in in-vitro cell assays have been reported, but translation to the clinic is hampered by poor in-vivo stability of nucleic acids and ineffective uptake of nucleic acids by target cells. This study aims to overcome these obstacles by designing, producing and testing in-vivo new miRNA targeting materials constituted by Peptide Nucleic Acids (PNAs, synthetic mimics of natural DNA and RNA) [1]. Indeed, PNAs conjugate the effectiveness of the natural nucleic acids targeting with chemical/thermal stability and resistance to enzymatic biodegradation. In order to follow the fate of PNA and improve its solubility and permeability to cells, PNA has been linked to superparamagnetic iron oxide nanoparticles (SPIONs), affording new nanocomposites which will be exploited both as contrast agents for magnetic resonance imaging (MRI) and as sources of local overheating through the application of an alternating magnetic filed (Magnetic Fluid Hyperthermia, MHF). SPIONs have been prepared by a slightly modified thermal decomposition method [2] in order to optimize in particular the hyperthermia effectiveness [3]. Then, the oleate layer has been exchanged with dimercaptosuccinic acid (DMSA) which is a bifunctional small molecule, able to efficiently substitute the oleate capping agent [4]. This way both COOH and SH groups can be exploited to link PNA to the NP surface. In this work the synthesis of the magnetic NPs, their characterization and their functionalization with PNA are presented. References [1] P. E. Nielsen, M. Egholm, R. H. Berg, O. Buchardt, Science, 254 (1991) 1497. [2] P. Calcagnile, D. Fragouli, I. S. Bayer, G. C. Anyfantis, L. Martiradonna, P. D. Cozzoli, R. Cingolani, A. Athanassiou, ACS Nano, 6 (2012) 5413. [3] G. F. Goya, V. Grazu, M. R. Ibarra, Curr. Nanosci., 4 (2008) 1. [4] A. Ruiz, P. C. Morais, R. Bentes de Azevedo, Z. G. M. Lacava, A. Villanueva, M. del Puerto Morales, J Nanopart. Res., 16 (2014) 2589.
Settore CHIM/03 - Chimica Generale e Inorganica
Iron Oxide-PNA nanoparticles for miRNA targeting / A. Maggioni, D. Dova, A. Guerrini, C. Carrara, P.R. Thakare, M. Galli, C. Sangregorio, S. Cauteruccio, M. Panigati, E. Licandro, R. Pennati, F. Orsini, P. Arosio, A. Lascialfari. ((Intervento presentato al convegno Trends in Nanotechnology International Conference tenutosi a Toulouse nel 2015.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/471610
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