Silica-Coated Metal Chelating-Melanin Nanoparticles as a Dual-Modal Contrast Enhancement Imaging and Therapeutic Agent

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• 作者：Soojeong Cho ; Wooram ParkDong-Hyun Kim
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2017
• 出版时间：January 11, 2017
• 年：2017
• 卷：9
• 期：1
• 页码：101-111
• 全文大小：688K
• ISSN：1944-8252

文摘

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@SiO₂ NP) with a modified sol–gel process. The silica nanocoating allowed increased outer sphere water diffusion time, resulting a significantly brighter MR T₁ contrast effect of Gd-Mel@SiO₂ NP, comparing with a bare Gd-Mel NP or clinical grade T₁ contrast agent. Further, when the Gd-Mel@SiO₂ NP 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@SiO₂ NPs were successfully evaluated in a clinically relevant human prostate cancer xenograft mouse model.