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Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium (III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode CT/MR imaging of lung cancer metastasis. In this present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r1 relaxivity (13.17 mM s-1), acceptable cytocompatibility and targeting specificity to αvβ3 integrin-expressing cancer cells, and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.
This article was published in the following journal.
Name: ACS applied materials & interfaces
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Gadolinium contrast agents are frequently administered for MRI imaging. Very little is known of its toxicity outside of patients with reduced renal function.
Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver.
Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.
Unstable isotopes of gold that decay or disintegrate emitting radiation. Au 185-196, 198-201, and 203 are radioactive gold isotopes.
Gadolinium. An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.
Stable gold atoms that have the same atomic number as the element gold, but differ in atomic weight. Au-197 is a stable isotope.
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