A novel efficient method has been developed for covalently linking Peptide Nucleic Acid (PNA) oligomers and superparamagnetic iron oxide nanoparticles (SPION), to produce water soluble hybrid nanomaterials that can act as MRI contrast agents, as hyperthermia promoters and as PNA carriers. The multistep procedure involves: (i) preparation of oleate-stabilized SPION by using the thermal decomposition method, to control the size of the magnetic core (here 17 ± 2 nm, by TEM measurement); (ii) exchange of the oleate layer by dimercaptosuccinic acid (DMSA), to impart water solubility and to provide functional groups for PNA grafting; (iii) functionalization of a PNA oligomer with a terminal maleimide moiety, to allow SPION-PNA conjugation by thiol-maleimide Michael addition reaction, exploiting the SH groups of DMSA on the SPION surface. The method was tested using a model PNA decamer containing all four nucleobases (-CTAGATCACT-). SPION-PNA conjugation by SH addition was found more efficient than conjugation through amide bond between the COOH groups of DMSA and the terminal NH2 groups of PNA. Elemental analysis, UV-Vis and IR spectra, and ζ-potential measures confirmed the PNA binding (a loading of ca. 400 PNA strands per SPION was estimated, molar ratio ca. 1 : 15 with respect to DMSA). A detailed characterization of the morphology, relaxivity and magnetic properties of the SPION used for PNA binding is reported, and compared to the one relative to the SPION-PNA conjugate. The analysis of the magnetic behaviour showed that the nanoparticles are in the superparamagnetic regime at room temperature, and have a considerably high saturation magnetization (85 emu g-1). Magnetic hyperthermia measurements gave a remarkable value of the heat released (SAR = 65 W g-1), which makes these SPION suitable for magnetic hyperthermia treatments. The SPION were also able to effectively shorten both longitudinal and transverse relaxation times of water, with r1 and r2 values higher with respect to routinely used commercial contrast agents, at the typical fields of clinical instrumentation.
Superparamagnetic iron oxide nanoparticles functionalized by peptide nucleic acids / M. Galli, A. Guerrini, S. Cauteruccio, P. Thakare, D. Dova, F. Orsini, P. Arosio, C. Carrara, C. Sangregorio, A. Lascialfari, D. Maggioni, E. Licandro. - In: RSC ADVANCES. - ISSN 2046-2069. - 7:25(2017), pp. 15500-15512.
|Titolo:||Superparamagnetic iron oxide nanoparticles functionalized by peptide nucleic acids|
GALLI, MARCO (Primo)
MAGGIONI, DANIELA (Corresponding)
LICANDRO, EMANUELA (Ultimo)
|Parole Chiave:||superparamagnetism; addition reactions; bins; decomposition; grafting (chemical); magnetism; saturation magnetization; metal nanoparticles;|
|Settore Scientifico Disciplinare:||Settore CHIM/03 - Chimica Generale e Inorganica|
Settore CHIM/06 - Chimica Organica
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1039/c7ra00519a|
|Appare nelle tipologie:||01 - Articolo su periodico|