Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, London, W12 0BZ, UK.
Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, SE1 7EH, UK.
Chemistry. 2020 Apr 6;26(20):4552-4566. doi: 10.1002/chem.201904757. Epub 2020 Mar 18.
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 ) per Gd unit from 5.01 mm s in unbound form to 31.68 mm s (10 MHz, 37 °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.
一种稳定的二硫代氨基甲酸盐连接物可以将基于 DOTAGA（q=1）的新型镧系元素单元连接到金纳米粒子（直径 2.6-4.1nm）的表面上，同时还可以连接提供生物相容性、靶向性和光动力治疗的功能单元。由于在纳米粒子表面上的受限旋转和镧系元素配合物的增强刚性，当固定在表面上时，每个镧系元素单元的弛豫率（r ）从游离形式的 5.01mm/s 急剧增加到 31.68mm/s（10MHz，37°C）。这种单步合成路线为制备多功能金纳米粒子提供了一种简单而通用的方法，包括与共轭锌四苯基卟啉光敏剂结合的例子。这些材料（MTT 测定）缺乏毒性，但在对 HeLa 细胞进行 30 分钟的光动力治疗（PDT）照射后，毒性会转化为 75%的细胞死亡。除了被动靶向外，包含能够主动靶向过表达叶酸受体的单元说明了这些组装体作为靶向治疗剂的潜力。
