Synthesis and characterization of multifunctional dendrimer-based organicinorganic hybrid nanopartic

来源 :2012上海市研究生学术论坛暨第三届上海交通大学医(理)工研究生学术论坛 | 被引量 : 0次 | 上传用户:michaelhocn
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Development of multifunctional multi-mode imaging nanoprobes for accurate diagnosis ofcancer still remains a great challenge. In this work, multifunctional dendrimer-based nanoparticles weresynthesized, characterized, and applied as a bimodal contrast agent for computed tomography(CT)/magnetic resonance (MR) imaging of cancer cells. The particles were synthesized usingamine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH2) pre-modified withgadolinium (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 byacetylation of the remaining dendrimer terminal amines. The formed multifunctional dendrimer-entrappedAu 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 stablein a pH range of 4~8 and in a temperature range of 0~50 ℃. MTT cytotoxicity assay along withcell morphology observation show that G5-Au/Gd-FA NPs are non-cytotoxic at the Au concentration ashigh as 100 μM. CT and T1-weighted MR measurements indicate that the G5-Au/Gd-FA NPs have a highX-ray attenuation intensity due to the presence of the dual radiodense element of Au and Gd, and displaygood r1 relaxivity due to the presence of the chelated Gd(III) ions. Combined inductively coupledplasma-atomic emission spectroscopic analysis of cellular upatke of Au element and in vitro CT andT1-weighted MR imgaing data show that the developed multifunctional particles are able to specificallytarget to cancer cells overexpressing high-affinity FA receptors in vitro. These findings indicate the greatpotential of the use of G5-Au/Gd-FA nanoprobe for dual mode targeted molecular imaging of cancer.
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