Zwitterionic Gadolinium(III)-Complexed Dendrimer-Entrapped Gold Nanoparticles for Enhanced Computed Tomography/Magnetic Resonance Imaging of Lung Cancer Metastasis

Abstract

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 the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimerentrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the 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 r 1 relaxivity (13.17 mM s −1 ), acceptable cytocompatibility, and targeting specificity to α v β 3 integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterionfunctionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.

Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo

“…Notably, one of the main benefits of the multi-modal imaging platform compared to single method imaging is the complementary aspect of the imaging agents. For example, a bi-modal CT/MRI conjugate can improve the imaging precision and the contrast enhancement compared to any singular imaging agent as shown with lung cancer [34]. Adding HER-2 targeting enhancement to these capabilities will substantially improve the utility of CT/MRI.…”

“…In addition, while published reports have documented ultrasound/MRI targeted imaging of HER-2 positive breast cancer cells, [35,36] we believe that this novel conjugate provides a more therapeutically meaningful option by combining CT and MRI targeted imaging for the early detection of HER-2 positive breast cancer. While most studies perform imaging 2-4 h after agent administration, [34,37] we have explored the pharmacokinetics of our conjugate for longer periods of time. From these results, specifically by the MRI data from our transgenic HER-2 mouse model, it shows persistence of signal enhancement out to 24 h after initial injection, similar to earlier time points at 4 and 8 h after injection for both CT and MRI.…”

Functionalization of Gold Nanoparticles by Inorganic Entities

“…These particles, suitable for dual imaging, exhibited a strong contrast enhancement in MRI stems. Other and recent works described Gd 3+ complexes for IRM applications [230][231][232]. Scheme 33.…”

Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment

“…Recently, GNPs have been developed to be used in dual mode techniques. In this regard, Liu et al [158] described the synthesis and use of zwitterionic Au dendrimers bound to targeting arginine-glycine-aspartic acid peptide and 2,2’,2’’-(10-(2- (2,5-dioxopyrrolidin-1-yloxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid/Gd(III) complexes in enhancing dual mode CT/MRI. This application of GNPs was validated in a B16 lung cancer metastasis model, with similar results being obtained with both imaging techniques.…”