Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units
Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units
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DOI：
10.1002/chem.201904757
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发表时间：
2020-03-18
影响因子：
4.3
通讯作者：
Wilton-Ely, James D. E. T.
中科院分区：
文献类型：
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作者：
Chabloz, Nicolas G.;Perry, Hannah L.;Wilton-Ely, James D. E. T.
坚固的二硫代氨基甲酸酯系链允许基于DOTAGA（q = 1）的新型钆单元与提供生物相容性、靶向和光动力疗法的功能单元一起附着到金纳米颗粒（2.6 - 4.1 nm直径）的表面。当固定在表面上时，由于纳米颗粒表面上Gd络合物的受限旋转和增强的刚性，观察到每个Gd单位的弛豫率（r（1））从未结合形式的5.01 mm（-1）s（-1）急剧增加到31.68 mm（-1）s（-1）（10 MHz，37 ℃）。一步合成路线提供了一个简单和通用的方法来制备多功能的金纳米粒子，包括共轭锌-四苯基卟啉光敏剂的例子。这些材料的毒性缺乏（MTT测定）在HeLa细胞照射30分钟（PDT）时转化，导致75%的细胞死亡。除了被动靶向之外，包含能够主动靶向过表达的叶酸受体的单元说明了这些组件作为靶向治疗诊断剂的潜力。
A robust dithiocarbamate tether allows novel gadolinium units based on DOTAGA (q=1) to be attached to the surface of gold nanoparticles (2.6-4.1 nm diameter) along with functional units offering biocompatibility, targeting and photodynamic therapy. A dramatic increase in relaxivity (r(1)) per Gd unit from 5.01 mm(-1) s(-1) in unbound form to 31.68 mm(-1) s(-1) (10 MHz, 37 degrees C) is observed when immobilised on the surface due to restricted rotation and enhanced rigidity of the Gd complex on the nanoparticle surface. The single-step synthetic route provides a straightforward and versatile way of preparing multifunctional gold nanoparticles, including examples with conjugated zinc-tetraphenylporphyrin photosensitizers. The lack of toxicity of these materials (MTT assays) is transformed on irradiation of HeLa cells for 30 minutes (PDT), leading to 75 % cell death. In addition to passive targeting, the inclusion of units capable of actively targeting overexpressed folate receptors illustrates the potential of these assemblies as targeted theranostic agents.