A Top-Down Synthesis Route to Ultrasmall Multifunctional Gd-Based Silica Nanoparticles for Theranostic Applications
A Top-Down Synthesis Route to Ultrasmall Multifunctional Gd-Based Silica Nanoparticles for Theranostic Applications
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DOI：
10.1002/chem.201203003
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发表时间：
2013-05-01
影响因子：
4.3
通讯作者：
Perriat, Pascal
中科院分区：
文献类型：
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作者：
Mignot, Anna;Truillet, Charles;Perriat, Pascal
已经获得了尺寸小于5纳米的新型超小纳米颗粒。这些小型刚性平台（SRP）由聚硅氧烷基质和DOTAGA（1,4,7,10-四氮杂环十二烷-1-戊二酸酐4,7,10-三乙酸）-Gd3+螯合物组成。它们是通过一个原始的自上而下的过程合成的：1)形成氧化钆Gd2O3核，2)封装在接枝DOTAGA配体的聚硅氧烷壳中，3)由于DOTAGA配体与Gd3+的螯合而溶解氧化钆核，4)聚硅氧烷碎裂。利用光子相关光谱（PCS）、透射电子显微镜（TEM）、超导量子干涉装置（SQUID）和电子顺磁共振（EPR）来证明氧化核的溶解，并通过电感耦合等离子体质谱（ICP-MS）、质谱、荧光光谱、Si-29固态核磁共振、H-1核磁共振和扩散有序光谱（DOSY）来确定纳米颗粒的组成。在60 MHz下，纵向弛豫度r(1)为11.9 s(-1)mm(-1) / Gd。最后，电位滴定表明Gd3+与DOTAGA强螯合（络合常数log β(110) = 24.78），细胞试验证实纳米结构具有非常低的毒性。此外，SRPs通过肾脏清除从体内排出。它们作为MRI造影剂的有效性已被证明，它们是图像引导放射治疗增敏剂的有希望的候选者。
New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetra-azacyclododecane-1-glutaric anhydride4,7,10-triacetic acid)-Gd3+ chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd3+ by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, Si-29 solid-state NMR, H-1 NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r(1) of 11.9 s(-1)mm(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd3+ is strongly chelated to DOTAGA (complexation constant log beta(110) = 24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.