Silica-Coated Metal Chelating-Melanin Nanoparticles as a Dual-Modal Contrast Enhancement Imaging and Therapeutic Agent.
Silica-Coated Metal Chelating-Melanin Nanoparticles as a Dual-Modal Contrast Enhancement Imaging and Therapeutic Agent.
复制标题
DOI：
10.1021/acsami.6b11304
复制
发表时间：
2017-01-11
影响因子：
9.5
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Cho S;Park W;Kim DH
利用多巴胺合成的生物激发黑色素纳米粒(MEL-NP)在各种生物医学领域的应用引起了人们的极大兴趣。然而，MEL NP固有的MR对比度效应、对金属离子的高亲和力、强的光吸收等迷人特性的利用，需要特殊的设计和策略性的合成方法来达到自己的目的。在这里，我们将顺磁性Gd3+金属离子和二氧化硅纳米涂层引入MEL纳米粒子，用于MRI/荧光对比增强成像和治疗的双模式。为提高MEL NP的磁共振成像增强性能，优化了溶液中Gd3+含量和pH条件下MEL NP与对苯二酚和对苯二酚残基螯合Gd3+的动力学。然后，采用改进的溶胶-凝胶法在Gd-Mel纳米粒子(Gd-Mel@SiO_2 NP)表面包覆生物惰性二氧化硅。与裸露的Gd-Mel NP或临床级T1造影剂相比，二氧化硅纳米涂层允许延长外球水扩散时间，导致Gd-Mel@SiO_2 NP的MR T1对比效果明显更亮。此外，当Gd-Mel@SiO_2纳米颗粒被荧光分子标记时，二氧化硅纳米涂层显著增强了荧光强度，防止了黑色素固有的荧光失活特性。最后，在临床相关的人前列腺癌异种移植小鼠模型中，成功地评估了体外/体内双模式对比增强MRI/荧光成像以及使用Gd-Mel@SiO_2纳米粒子进行图像引导癌症治疗应用的可行性。
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.
登录
查看更多内容
影响因子：
15
作者：
FELIX, CC;HYDE, JS;SEALY, RC
通讯作者：
SEALY, RC
影响因子：
4.8
作者：
Elhawary, Haytham;Oguro, Sota;Hata, Nobuhiko
通讯作者：
Hata, Nobuhiko
影响因子：
3.9
作者：
Dreyer, Daniel R.;Miller, Daniel J.;Bielawski, Christopher W.
通讯作者：
Bielawski, Christopher W.
影响因子：
15
作者：
Janjic, Jelena M.;Srinivas, Mangala;Ahrens, Eric T.
通讯作者：
Ahrens, Eric T.
影响因子：
--
作者：
Godechal, Q.;Mignion, L.;Gallez, B.
通讯作者：
Gallez, B.