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 dendrimer-entrapped 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 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.

• Authors: Jinyuan Liu, Zhijuan Xiong, Jiulong Zhang, Chen Peng, Barbara Klajnert-Maculewicz, Mingwu Shen, Xiangyang Shi
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 11 Issue 17 Pg. 15212-15221 (May 01 2019) ISSN: 1944-8252 [Electronic] United States
• PMID: 30964632 (Publication Type: Journal Article)

Chemical References

• Contrast Media
• Coordination Complexes
• Dendrimers
• Heterocyclic Compounds, 1-Ring
• Oligopeptides
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Gold
• arginyl-glycyl-aspartic acid
• Gadolinium

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Contrast Media (chemistry, toxicity)
• Coordination Complexes (chemistry)
• Dendrimers (chemistry)
• Gadolinium (chemistry)
• Gold (chemistry)
• Heterocyclic Compounds, 1-Ring (chemistry)
• Humans
• Lung Neoplasms (diagnosis, diagnostic imaging, secondary)
• Magnetic Resonance Imaging
• Melanoma, Experimental (pathology)
• Metal Nanoparticles (chemistry)
• Mice
• Oligopeptides (chemistry)
• RAW 264.7 Cells
• Signal-To-Noise Ratio
• Tomography, X-Ray Computed
• Transplantation, Homologous