The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Department of Chemistry, Shanghai Normal University, No.100 Guilin Road, Shanghai, 200234, China.
Nanoscale. 2013 Nov 7;5(21):10447-54. doi: 10.1039/c3nr03490a. Epub 2013 Sep 13.
The objective of this study was to evaluate the targeted T1-magnetic resonance imaging (MRI), quantitative biodistribution and toxicity of aptamer (AS411) conjugated Mn3O4@SiO2 core-shell nanoprobes (NPs) in human cervical carcinoma tumor-bearing mice. The NPs were firstly prepared by encapsulating a hydrophobic Mn3O4 core within an amino functionalized silica shell. The fluorophore rhodamine (RB) was doped into the silica shell and the amphiphilic polymer poly(ethylene glycol) (PEG) was modified on the surface of the shell to improve its biocompatibility, then the aptamer AS411 was conjugated onto the end of the PEG chains as targeting ligands. The final NPs were abbreviated as Mn3O4@SiO2(RB)-PEG-Apt. By means of in vitro fluorescence confocal imaging and in vivo MRI, the NPs have been demonstrated to target cancer cells and prominent tumor aggregation effectively. The imaging results were further confirmed by a quantitative biodistribution study. In addition, histological, hematological and biochemistry analysis also proved the low toxicity of NPs in vivo. Our results showed the great potential of the Mn3O4@SiO2(RB)-PEG-Apt NPs could be used as a multifunctional nanoplatform for long-term targeted imaging and therapy of cancer.
本研究旨在评估靶向 T1 磁共振成像(MRI)、定量生物分布和毒性的适体(AS411)偶联 Mn3O4@SiO2 核壳纳米探针(NPs)在人宫颈癌荷瘤小鼠中的应用。NPs 首先通过在氨基功能化的硅壳内包裹疏水性 Mn3O4 核来制备。荧光染料罗丹明(RB)被掺杂到硅壳中,亲水性聚合物聚乙二醇(PEG)被修饰到壳的表面以提高其生物相容性,然后将适体 AS411 偶联到 PEG 链的末端作为靶向配体。最终的 NPs 被缩写为 Mn3O4@SiO2(RB)-PEG-Apt。通过体外荧光共聚焦成像和体内 MRI,证明 NPs 能够有效地靶向癌细胞并显著聚集肿瘤。成像结果进一步通过定量生物分布研究得到证实。此外,组织学、血液学和生物化学分析也证明了 NPs 在体内的低毒性。我们的结果表明,Mn3O4@SiO2(RB)-PEG-Apt NPs 具有作为多功能纳米平台用于癌症的长期靶向成像和治疗的巨大潜力。