title: A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.
abstract: The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Center for Bionanoengineering and State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: zxl125@case.edu.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D039302:Integrin alphaVbeta3 / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D049329:Nanostructures / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D047392:beta-Cyclodextrins; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
keywords: Cancer molecular imaging; Cyclodextrin; Gadolinium contrast agent; Host-guest interaction; Magnetic resonance imaging; α(v)β(3) integrin