Concept In the last decade magnetic nanoparticles (NPs), had a large impact in many areas of biomedicine, including contrast agents for magnetic resonance imaging, drug targeting, diagnostics, molecular biology, cell separation and purification, and hyperthermia therapy. In this widespread scenario we started a project aimed to design new biocompatible materials based on magnetic NPs allowing a two-fold anticancer action, i.e. capable of combining the therapeutic effect based on targeted drug-delivery with hyperthermia for the treatment of widespread diseases. Moreover in designing these new systems, enhanced relaxometric properties will be also pursed, in order follow the biodistribution of the carriers inside human body and inside tumoral cells by MR imaging. Motivations and Objectives The main goal of the project is the development of a new class of innovative nanodevices based on iron oxide magnetic nanoparticles (MNP), with multi-fold therapeutic and diagnostic applications. To this end, the first step is represented by the synthesis of novel biocompatible, biodegradable, poly(amidoamine) (PAA) nanovectors embedding a nanometric (10-20 nm) magnetite/maghemite core. PAA are a family of synthetic polymers with many relevant properties useful for biomedical applications[1]. Moreover, PAA can be easily functionalized by introducing multidentate ligands to act as chelating polymers for MNP. In order to improve the stability of the nanovectores, block copolymer of PAA and poly(ethyleneglycol) (PEG) were prepared and tested. Results and Discussion PAA chelating ligands for MNP were prepared using N,N’-ethylenediamine disuccinic acid (EDDS and PAA-PEG block copolymers were prepared by direct polymerization of PEG-NH2 and PEG-piperazine as aminic-comonomers in the synthesis of PAA-EDDS polymers. Monodisperse Fe3O4 NPs of different average size were prepared by thermal decomposition of a solution of Fe(oleate)3 precursor and oleic acid in octadecene. The morphological and structural characterization of the NPs confirmed that uniform spherical magnetite/maghemite NPs with average size 10.1±2 nm and 17.5±2.5 nm were formed. The obtained NPs were then embedded into PEG-piperazine-PAA-EDDS and PEG-NH2-PAA-EDDS copolymers by ligand exchange reaction carried out in a toluene:DMSO 4:1 solution. The synthesized nano-objects could be fully dispersed in water at physiological conditions, forming colloids that are stable over very long periods. The aqueous solutions were then deeply investigated for their static and dynamic magnetic properties which showed room temperature superparamagnetic behavior and high magnetic moment. AC susceptibility measurements showed the samples have non-zero out-of-phase susceptibility at 300 K. All these properties make our systems good candidates for the proposed clinical applications. The preliminary evaluation of the hyperthermic and relaxometric efficacies, performed by standard calorimetric and NMR-D measurements confirms this indication.

Novel multifunctional nanovectors based on iron oxide nanoparticles and poly(amidomine)s / F. Fenili, E. Ranucci, A.G. Manfredi, P. Ferruti, L.I. Cabrera, C. Innocenti, C. Sangregorio, A. Lascialfari. ((Intervento presentato al 8. convegno Convegno nazionale INSTM sulla scienza e tecnologia dei materiali tenutosi a Aci Castello (CT) nel 2011.

Novel multifunctional nanovectors based on iron oxide nanoparticles and poly(amidomine)s

F. Fenili;E. Ranucci;A.G. Manfredi;P. Ferruti;A. Lascialfari
2011-06-26

Abstract

Concept In the last decade magnetic nanoparticles (NPs), had a large impact in many areas of biomedicine, including contrast agents for magnetic resonance imaging, drug targeting, diagnostics, molecular biology, cell separation and purification, and hyperthermia therapy. In this widespread scenario we started a project aimed to design new biocompatible materials based on magnetic NPs allowing a two-fold anticancer action, i.e. capable of combining the therapeutic effect based on targeted drug-delivery with hyperthermia for the treatment of widespread diseases. Moreover in designing these new systems, enhanced relaxometric properties will be also pursed, in order follow the biodistribution of the carriers inside human body and inside tumoral cells by MR imaging. Motivations and Objectives The main goal of the project is the development of a new class of innovative nanodevices based on iron oxide magnetic nanoparticles (MNP), with multi-fold therapeutic and diagnostic applications. To this end, the first step is represented by the synthesis of novel biocompatible, biodegradable, poly(amidoamine) (PAA) nanovectors embedding a nanometric (10-20 nm) magnetite/maghemite core. PAA are a family of synthetic polymers with many relevant properties useful for biomedical applications[1]. Moreover, PAA can be easily functionalized by introducing multidentate ligands to act as chelating polymers for MNP. In order to improve the stability of the nanovectores, block copolymer of PAA and poly(ethyleneglycol) (PEG) were prepared and tested. Results and Discussion PAA chelating ligands for MNP were prepared using N,N’-ethylenediamine disuccinic acid (EDDS and PAA-PEG block copolymers were prepared by direct polymerization of PEG-NH2 and PEG-piperazine as aminic-comonomers in the synthesis of PAA-EDDS polymers. Monodisperse Fe3O4 NPs of different average size were prepared by thermal decomposition of a solution of Fe(oleate)3 precursor and oleic acid in octadecene. The morphological and structural characterization of the NPs confirmed that uniform spherical magnetite/maghemite NPs with average size 10.1±2 nm and 17.5±2.5 nm were formed. The obtained NPs were then embedded into PEG-piperazine-PAA-EDDS and PEG-NH2-PAA-EDDS copolymers by ligand exchange reaction carried out in a toluene:DMSO 4:1 solution. The synthesized nano-objects could be fully dispersed in water at physiological conditions, forming colloids that are stable over very long periods. The aqueous solutions were then deeply investigated for their static and dynamic magnetic properties which showed room temperature superparamagnetic behavior and high magnetic moment. AC susceptibility measurements showed the samples have non-zero out-of-phase susceptibility at 300 K. All these properties make our systems good candidates for the proposed clinical applications. The preliminary evaluation of the hyperthermic and relaxometric efficacies, performed by standard calorimetric and NMR-D measurements confirms this indication.
Settore CHIM/05 - Scienza e Tecnologia dei Materiali Polimerici
Consorzio Interuniversitario Nazionale per la Scienza e la Tecnologia dei Materiali
Novel multifunctional nanovectors based on iron oxide nanoparticles and poly(amidomine)s / F. Fenili, E. Ranucci, A.G. Manfredi, P. Ferruti, L.I. Cabrera, C. Innocenti, C. Sangregorio, A. Lascialfari. ((Intervento presentato al 8. convegno Convegno nazionale INSTM sulla scienza e tecnologia dei materiali tenutosi a Aci Castello (CT) nel 2011.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/162794
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