title: Silica-Coated Metal Chelating-Melanin Nanoparticles as a Dual-Modal Contrast Enhancement Imaging and Therapeutic Agent.
abstract: Bioinspired melanin nanoparticle (Mel NP) synthesized with dopamine has been of great interest in various biomedical applications. However, the utilization of fascinating characters of Mel NP such as innate MR contrast effects, high affinity to metal ions, strong light absorption requires special design with strategic synthetic method for its own purpose. Here, we have introduced paramagnetic Gd3+metal ions and silica nanocoating on Mel NP for the dual-modal MRI/fluorescent contrast-enhanced imaging and therapeutics. The Gd3+chelating kinetics of Mel NP by quinone and hydroquinone residues were optimized in various conditions of Gd3+amounts and pH in solution for improving MRI contrast enhancing properties of the Mel NP. Then, bioinert silica was coated on the surfaces of Gd-chelated Mel NP (Gd-Mel@SiO2NP) with a modified sol-gel process. The silica nanocoating allowed increased outer sphere water diffusion time, resulting a significantly brighter MR T1contrast effect of Gd-Mel@SiO2NP, comparing with a bare Gd-Mel NP or clinical grade T1contrast agent. Further, when the Gd-Mel@SiO2NP was labeled with fluorescent molecules, a significantly enhanced fluorescent intensity was achieved by the silica nanocoating that preventing the innate fluorescent deactivation property of melanin. Finally, in vitro/in vivo dual-modal contrast enhanced MRI/fluorescent imaging and feasibility of image-guided cancer therapeutic applications using Gd-Mel@SiO2NPs were successfully evaluated in a clinically relevant human prostate cancer xenograft mouse model.
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Soojeong
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Wooram
authors.identifier: 0000-0002-4614-0530
authors.initials: W
authors.lastname: Park
authors.affiliation: Department of Radiology, Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States.|Robert H. Lurie Comprehensive Cancer Center , Chicago, Illinois 60611, United States.
authors.forename: Dong-Hyun
authors.identifier: 0000-0001-6815-3319
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003287:Contrast Media; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008543:Melanins; D053768:Metal Nanoparticles; D051379:Mice; D053758:Nanoparticles; D012822:Silicon Dioxide
chemical_list: D003287:Contrast Media; D008543:Melanins; D012822:Silicon Dioxide
keywords: MRI; fluorescence imaging; melanin; metal-chelation; multimodal image-guidance; silica coating