Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging
Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging
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DOI：
10.1021/bc060269t
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发表时间：
2007-07-01
影响因子：
4.7
通讯作者：
Delville, Marie-Héléne
中科院分区：
文献类型：
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作者：
Voisin, Pierre;Ribot, Emeline Julie;Delville, Marie-Héléne
常用的基于Gd 3+的MRI试剂的改进需要设计具有优化的体内功效、药代动力学性质和特异性的新系统。为了设计这些造影剂，通常考虑两个参数：增加配位水分子的数量或通过增加分子量和尺寸来增加旋转相关时间。这已经通过低分子量Gd 3+螯合物与大分子或聚合物的非共价或共价结合来实现。提出了将这些高自旋顺磁钆螯合物接枝到金属氧化物纳米颗粒（SiO2，Al 2 O3）上。这种新的合成策略呈现出至少两个主要优点：（1）MRI的高T-1弛豫率，MRI信号增加275%，以及（2）纳米颗粒在细胞中内化的能力。结果表明，这些新的造影剂导致小胶质细胞内的Gd 3+顺磁性物质的巨大再集中。这种再浓缩现象导致高的信号-噪声比的细胞的MR图像颗粒内化后，从1.4到3.75，分别使用Al 2 O3或SiO2颗粒。这些新粒子的性质将进一步用于获得对神经胶质瘤基因治疗的新见解，使用小胶质细胞作为载体，同时运输自杀基因和造影剂。由于小胶质细胞被化学吸引到脑肿瘤，这些新的造影剂在细胞内的存在将导致更好的MRI确定肿瘤的体内位置，形状和边界。因此，这些Gd 3+负载的小胶质细胞可以在应用任何治疗性治疗之前通过MRI提供肿瘤的有效定位。自杀基因策略后的癌症缓解率也是可能的。
The improvement of commonly used Gd3+-based MRI agents requires the design of new systems with optimized in vivo efficacy, pharmacokinetic properties, and specificity. To design these contrast agents, two parameters are usually considered: increasing the number of coordinated water molecules or increasing the rotational correlation time by increasing molecular weight and size. This has been achieved by noncovalent or covalent binding of low-molecular weight Gd3+ chelates to macromolecules or polymers. The grafting of these high-spin paramagnetic gadolinium chelates on metal oxide nanoparticles (SiO2, Al2O3) is proposed. This new synthetic strategy presents at least two main advantages: (1) a high T-1-relaxivity for MRI with a 275% increase of the MRI signal and (2) the ability of nanoparticles to be internalized in cells. Results indicate that these new contrast agents lead to a huge reconcentration of Gd3+ paramagnetic species inside microglial cells. This reconcentration phenomenon gives rise to high signal-to-noise ratios on MR images of cells after particle internalization, from 1.4 to 3.75, using Al2O3 or SiO2 particles, respectively. The properties of these new particles will be further used to get new insight into gene therapy against glioma, using microglial cells as vehicles to simultaneously transport a suicide gene and contrast agents. Since microglia are chemoattracted to brain tumors, the presence of these new contrast agents inside the cells will lead to a better MRI determination of the in vivo location, shape, and borders of the tumors. These Gd3+-loaded microglia can therefore provide effective localization of tumors by MRI before applying any therapeutic treatment. The rate of carcinoma remission following a suicide gene strategy is also possible.