Noninvasive MRI-SERS imaging in living mice using an innately bimodal nanomaterial.

We report a novel nanomaterial (AuMN-DTTC) that can be used as a bimodal contrast agent for in vivo magnetic resonance imaging (MRI) and Raman spectroscopy. The probe consists of MRI-active superparamagnetic iron oxide nanoparticles, stably complexed with gold nanostructures. The gold component serves as a substrate for a Raman active dye molecule to generate a surface-enhanced Raman scattering (SERS) effect. The synthesized probe produces T2 weighted contrast and can be used as a SERS active material both in silico (in aqueous solution) and in vivo. A quantitative assessment of T2 relaxation times was obtained using multiecho MRI analysis. The T2 relaxation times of AuMN-DTTC and MN (dextran-coated iron oxide nanoparticles) were 29.23 + 1.45 and 31.58 + 1.7 ms, respectively. The SERS signature of AuMN-DTTC revealed peaks at 508, 629, 782, 844, 1080, 1108, 1135, and 1242 cm(-1). Intramuscular administration of the probe resulted in a decrease of the T2 relaxation time of muscle from 33.4 + 2.5 to 20.3 + 2.2 ms. SERS peaks were observed at 508, 629, 782, 844, 1080, 1108, 1135, and 1242 cm(-1), consistent with the in silico results. Our studies illustrate for the first time the design and in vivo application of a contrast agent, whose component modalities include MRI and SERS. The value of this agent lies in its innately bimodal nature and its application in vivo for molecular imaging applications.

[1]  R. Dasari,et al.  Single Molecule Detection Using Surface-Enhanced Raman Scattering (SERS) , 1997 .

[2]  Chad A. Mirkin,et al.  One-Pot Colorimetric Differentiation of Polynucleotides with Single Base Imperfections Using Gold Nanoparticle Probes , 1998 .

[3]  Xueding Wang,et al.  Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[4]  Ralph Weissleder,et al.  DNA-based magnetic nanoparticle assembly acts as a magnetic relaxation nanoswitch allowing screening of DNA-cleaving agents. , 2002, Journal of the American Chemical Society.

[5]  Donghoon Lee,et al.  Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles. , 2008, Nanomedicine.

[6]  Anna Moore,et al.  Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging. , 2009, Cancer research.

[7]  Ralph Weissleder,et al.  Magnetic Nanosensors for the Detection of Oligonucleotide Sequences. , 2001, Angewandte Chemie.

[8]  Zhichuan J. Xu,et al.  Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties. , 2007, Journal of the American Chemical Society.

[9]  Yi Lu,et al.  Adenosine-dependent assembly of aptazyme-functionalized gold nanoparticles and its application as a colorimetric biosensor. , 2004, Analytical chemistry.

[10]  Luis M Liz-Marzán,et al.  Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. , 2009, Journal of the American Chemical Society.

[11]  C. Niemeyer REVIEW Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science , 2022 .

[12]  Ralph Weissleder,et al.  Magnetic relaxation switch immunosensors detect enantiomeric impurities. , 2004, Angewandte Chemie.

[13]  Ralph Weissleder,et al.  Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. , 2003, The New England journal of medicine.

[14]  Anna Moore,et al.  In vivo imaging of siRNA delivery and silencing in tumors , 2007, Nature Medicine.

[15]  Shuming Nie,et al.  Spectroscopic tags using dye-embedded nanoparticles and surface-enhanced Raman scattering. , 2003, Analytical chemistry.

[16]  L. Liz‐Marzán,et al.  Bifunctional Nanocomposites with Long-Term Stability as SERS Optical Accumulators for Ultrasensitive Analysis , 2009 .

[17]  Steven R. Emory,et al.  Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering , 1997, Science.

[18]  Jayanth Panyam,et al.  Biodegradable nanoparticles for drug and gene delivery to cells and tissue. , 2003, Advanced drug delivery reviews.

[19]  Catherine C. Berry,et al.  Functionalisation of magnetic nanoparticles for applications in biomedicine : Biomedical applications of magnetic nanoparticles , 2003 .

[20]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[21]  Juewen Liu,et al.  Fast colorimetric sensing of adenosine and cocaine based on a general sensor design involving aptamers and nanoparticles. , 2005, Angewandte Chemie.

[22]  Duncan Graham,et al.  Rapid and ultra-sensitive determination of enzyme activities using surface-enhanced resonance Raman scattering , 2004, Nature Biotechnology.

[23]  Jeff W M Bulte,et al.  Iron oxide MR contrast agents for molecular and cellular imaging , 2004, NMR in biomedicine.

[24]  Yi Lu,et al.  A colorimetric lead biosensor using DNAzyme-directed assembly of gold nanoparticles. , 2003, Journal of the American Chemical Society.

[25]  Yi Lu,et al.  MRI detection of thrombin with aptamer functionalized superparamagnetic iron oxide nanoparticles. , 2008, Bioconjugate chemistry.

[26]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[27]  Chitta Ranjan Patra,et al.  Fabrication of gold nanoparticles for targeted therapy in pancreatic cancer. , 2010, Advanced drug delivery reviews.

[28]  Ralph Weissleder,et al.  Magnetic relaxation switches capable of sensing molecular interactions , 2002, Nature Biotechnology.

[29]  Dohyung Lim,et al.  Heparin-coated gold nanoparticles for liver-specific CT imaging. , 2009, Chemistry.

[30]  Michael J. Welch,et al.  In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. , 2010, Bioconjugate chemistry.

[31]  Kai Chen,et al.  PET/NIRF/MRI triple functional iron oxide nanoparticles. , 2010, Biomaterials.

[32]  Anna Moore,et al.  In vivo imaging of islet transplantation , 2006, Nature Medicine.

[33]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[34]  A. Campion,et al.  Surface-enhanced Raman scattering , 1998 .

[35]  B Merchant,et al.  Gold, the noble metal and the paradoxes of its toxicology. , 1998, Biologicals : journal of the International Association of Biological Standardization.

[36]  Chad A Mirkin,et al.  Three-layer composite magnetic nanoparticle probes for DNA. , 2005, Journal of the American Chemical Society.

[37]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[38]  Louis E. Brus,et al.  Surface Enhanced Raman Spectroscopy of Individual Rhodamine 6G Molecules on Large Ag Nanocrystals , 1999 .

[39]  G A ANDREWS,et al.  The distribution and radiation effects of intravenously administered colloidal Au198 in man , 1954, Cancer.

[40]  J. Storhoff,et al.  A DNA-based method for rationally assembling nanoparticles into macroscopic materials , 1996, Nature.

[41]  G. Dai,et al.  In vivo multimodal imaging of transplanted pancreatic islets , 2006, Nature Protocols.

[42]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[43]  K. S. Shin,et al.  Silanization of Ag-deposited magnetite particles: an efficient route to fabricate magnetic nanoparticle-based Raman barcode materials. , 2010, ACS applied materials & interfaces.

[44]  Raoul Kopelman,et al.  Targeted gold nanoparticles enable molecular CT imaging of cancer. , 2008, Nano letters.

[45]  Ralph Weissleder,et al.  Emerging concepts in molecular MRI. , 2007, Current opinion in biotechnology.

[46]  M. Shoichet,et al.  de Doxorubicin-Conjugated Immuno-Nanoparticles for Intracellular Anticancer Drug Delivery P E R , 2009 .

[47]  Yi Lu,et al.  Smart “Turn‐on” Magnetic Resonance Contrast Agents Based on Aptamer‐Functionalized Superparamagnetic Iron Oxide Nanoparticles , 2007, Chembiochem : a European journal of chemical biology.

[48]  R. Dasari,et al.  Ultrasensitive Chemical Analysis by Raman Spectroscopy , 1999 .

[49]  P. Alivisatos The use of nanocrystals in biological detection , 2004, Nature Biotechnology.