Synthesis and Characterization of Multifunctional Dendrimer-based Organic/Inorganic Hybrid Nanoparticles for Dual Mode CT/MR Imaging Applications

摘要

Development of multifunctional multi-mode imaging nanoprobes for accurate diagnosis of cancer still remains a great challenge.In this work,multifunctional dendrimer-based nanoparticles were synthesized,characterized,and applied as a bimodal contrast agent for computed tomography (CT)/magnetic resonance (MR) imaging of cancer cells.The particles were synthesized using amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH2) pre-modified with gadolinium (Gd) chelator (DOTA-NHS),polyethylene glycol (PEG) monomethyl ether,and PEG-folic acid (PEG-FA) conjugate as templates to entrap gold nanoparticles and chelate Gd(Ⅲ) ions,followed by acetylation of the remaining dendrimer terminal amines.The formed multifunctional dendrimer-entrapped Au nanoparticles (Au DENPs) (G5-Au/Gd-FA NPs) were characterized by UV-Vis spectrometry,1H NMR,and transmission electron microscopy.We show that the G5-Au/Gd-FA NPs are water soluble and stable in a pH range of 4-8 and in a temperature range of 0-50°C.MTT cytotoxicity assay along with cell morphology observation show that G5-Au/Gd-FA NPs are non-cytotoxic at the Au concentration as high as 100 μm.CT and T1-weighted MR measurements indicate that the G5-Au/Gd-FA NPs have a high X-ray attenuation intensity due to the presence of the dual radiodense element of Au and Gd,and display good r1 relaxivity due to the presence of the chelated Gd(Ⅲ) ions.Combined inductively coupled plasma-atomic emission spectroscopic analysis of cellular uptake of Au element and In vitro CT and T1-weighted MR imaging data show that the developed multifunctional particles are able to specifically target to cancer cells overexpressing high-affinity FA receptors In vitro.These findings indicate the great potential of the use of G5-Au/Gd-FA nanoprobes for dual mode targeted molecular imaging of cancer.