Aptamer-conjugated Mn3O4@SiO2 core-shell nanoprobes for targeted magnetic resonance imaging.

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.

[1]  G. Brudvig,et al.  Biocompatible and pH-sensitive PLGA encapsulated MnO nanocrystals for molecular and cellular MRI. , 2011, ACS nano.

[2]  Tao Chen,et al.  Aptamer-conjugated nanomaterials for bioanalysis and biotechnology applications. , 2011, Nanoscale.

[3]  Sung Tae Kim,et al.  Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. , 2007, Angewandte Chemie.

[4]  C. Robic,et al.  Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. , 2008, Chemical reviews.

[5]  Yun Sun,et al.  Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. , 2011, Biomaterials.

[6]  Xiaoxia Du,et al.  Silica‐Coated Manganese Oxide Nanoparticles as a Platform for Targeted Magnetic Resonance and Fluorescence Imaging of Cancer Cells , 2010 .

[7]  Lianghai Hu,et al.  Aptamer in bioanalytical applications. , 2011, Analytical chemistry.

[8]  Su He Wang,et al.  Dendrimer‐Functionalized Iron Oxide Nanoparticles for Specific Targeting and Imaging of Cancer Cells , 2007 .

[9]  Taeghwan Hyeon,et al.  Inorganic Nanoparticles for MRI Contrast Agents , 2009 .

[10]  Bongsoo Kim,et al.  Size-dependent magnetic properties of colloidal Mn(3)O(4) and MnO nanoparticles. , 2004, Angewandte Chemie.

[11]  Mingyuan Gao,et al.  Superparamagnetic iron oxide nanoparticles: from preparations to in vivo MRI applications , 2009 .

[12]  Weihong Tan,et al.  Aptamer-assembled nanomaterials for biosensing and biomedical applications. , 2011, Small.

[13]  Indrajit Roy,et al.  In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles. , 2010, ACS nano.

[14]  In Su Lee,et al.  Development of target-specific multimodality imaging agent by using hollow manganese oxide nanoparticles as a platform. , 2011, Chemical communications.

[15]  Wei Zheng,et al.  Manganese toxicity upon overexposure , 2004, NMR in biomedicine.

[16]  John O Trent,et al.  Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. , 2009, Experimental and molecular pathology.

[17]  Mingwu Shen,et al.  Facile assembly of Fe3O4@Au nanocomposite particles for dual mode magnetic resonance and computed tomography imaging applications , 2012 .

[18]  Zhen Cheng,et al.  HSA coated MnO nanoparticles with prominent MRI contrast for tumor imaging. , 2010, Chemical communications.

[19]  Won Jun Kang,et al.  Multiplex imaging of single tumor cells using quantum-dot-conjugated aptamers. , 2009, Small.

[20]  Enzo Terreno,et al.  Challenges for molecular magnetic resonance imaging. , 2010, Chemical reviews.

[21]  T. Hyeon,et al.  Nanostructured T1 MRI contrast agents , 2009 .

[22]  Shouheng Sun,et al.  One-pot synthesis of hollow/porous Mn-based nanoparticles via a controlled ion transfer process. , 2011, Chemical communications.

[23]  Su He Wang,et al.  Dendrimer‐Functionalized Shell‐crosslinked Iron Oxide Nanoparticles for In‐Vivo Magnetic Resonance Imaging of Tumors , 2008 .

[24]  Taeghwan Hyeon,et al.  Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. , 2009, Chemical Society reviews.

[25]  In Su Lee,et al.  Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. , 2009, Angewandte Chemie.

[26]  C. Yeh,et al.  The characteristics of sub 10 nm manganese oxide T1 contrast agents of different nanostructured morphologies. , 2010, Biomaterials.

[27]  Jie Liang,et al.  Facile synthesis of amino-functionalized hollow silica microspheres and their potential application for ultrasound imaging. , 2011, Journal of colloid and interface science.

[28]  Samuel A Wickline,et al.  Manganese-based MRI contrast agents: past, present and future. , 2011, Tetrahedron.