Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
,
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
,
Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA
,
Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School and Massachusetts General Hospital, Boston, USA
,
Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA
,
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
,
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
,
NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
1 NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
2 NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
3 Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA
4 Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School and Massachusetts General Hospital, Boston, USA
5 Athinoula A. Martinos Center of Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, USA
6 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
7 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA
8 NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, USA
MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.
KeywordsPositive ContrastTransverse Relaxation in the Rotating Frame (T2r)Superparamagnetic Iron-Oxide (Uspio)BurnSkeletal MuscleC-Fos
X. Fu, et al., “Thermal Injuries Induce Gene Expression of Endogenous C-Fos, C-Myc and bFgf in Burned Tissues,” Chinese Medical Journal, Vol. 116, No. 2, 2003, pp. 235-238.
X. Gu, et al., “mRNA and Protein Expression of Transcription Factor c-Fos in Burned Rats and Their Effects on Wound Healing,” Chinese Journal of Traumatol, Vol. 3, No. 3, 2000, pp. 141-145.
Q. Guo, Y. Hei and Y. Chen, “The Significance of the Postburn Expression of Proto-Oncogenes C-Fos and C-Myc mRNA and Proteins in Rat Myocardial Cells,” Chinese Journal of Burns, Vol. 17, No. 1, 2001, pp. 42-45.
A. Medina, et al., “The Role of Stratifin in Fibroblast-Keratinocyte Interaction,” Molecular andl Cellular Biochemisrty, Vol. 305, No. 1-2, 2007, pp. 255-264.
J. Chen, J. H. Wang and J. L. Ren, “Changes in the Expression of Apoptotic Genes in the Intestinal Tissue of Scalded Rats before and after Resuscitation,” Chinese Journal of Burns, Vol. 21, No. 1, 2005, pp. 55-56.
K. Cho, et al., “CD14and Toll-Like Receptor 4-Dependent Regulation of C-Fos, C-Jun and C-Jun Phosphorylation in the Adrenal Gland after Burn Injury,” Pathobiology, Vol. 71, No. 6, 2004, pp. 302-307.
C. H. Liu, et al., “Forebrain Ischemia-Reperfusion Simulating Cardiac Arrest in Mice Induces Edema and DNA Fragmentation in the Brain,” Molecular Imaging, Vol. 6, No. 3, 2007, pp. 156-170.
C. H. Liu, et al., “MR Contrast Probes That Trace Gene Transcripts for Cerebral Ischemia in Live Animals,” Official Publication of the Federation of American Societies for Experimental Biology, Vol. 21, No. 11, 2007, pp. 3004-3015.
C. H. Liu, et al., “Imaging Cerebral Gene Transcripts in Live Animals,” Journal of Neuroscience, Vol. 27, No. 3, 2007, pp. 713-722.
M. L. Oshinsky and J. Luo, “Neurochemistry of Trigeminal Activation in an Animal Model of Migraine,” Headache, Vol. 46, No. S1, 2006, pp. S39-44.
J. K. Higa and J. Panee, “Bamboo Extract Reduces Interleukin 6 (IL-6) Overproduction under Lipotoxic Conditions through Inhibiting the Activation of NF-KappaB and AP-1 Pathways,” Cytokine, Vol. 55, No. 1, 2011, pp. 18-23.
T. Wang, et al., “On the Mechanism of Targeting of Phage Fusion Protein-Modified Nanocarriers: Only the Binding Peptide Sequence Matters,” Molecular Pharmacetics, 2011. Vol. 8, No. 5, pp. 1720-1728
T. Wang, et al., “In vitro Optimization of Liposomal Nanocarriers Prepared from Breast Tumor Cell Specific Phage Fusion Protein,” Journal of Drug Targeting, Vol. 19, No. 8, 2011, pp. 597-605.
T. Wang, et al., “Enhanced Binding and Killing of Target Tumor Cells by Drug-Loaded Liposomes Modified with Tumor-Specific Phage Fusion Coat Protein,” Nanomedicine (Lond), Vol. 5, No. 4, 2010, pp. 563-574.
Y. T. Ko, C. Falcao and V. P. Torchilin, “Cationic Liposomes Loaded with Proapoptotic Peptide D-(KLAKLAK) (2) and Bcl-2 Antisense Oligodeoxynucleotide G3139 for Enhanced Anticancer Therapy,” Molecular Pharmacetics, Vol. 6, No. 3, 2009, pp. 971-977.
Y. T. Ko, et al., “Gene Delivery into Ischemic Myocardium by Double-Targeted Lipoplexes with Anti-Myosin Antibody and TAT Peptide,” Gene Therapy, Vol. 16, No. 1, 2009, pp. 52-59.
Y. T. Ko, et al., “Self-Assembling Micelle-Like Nanoparticles Based on Phospholipid-Polyethyleneimine Conjugates for Systemic Gene Delivery,” Journal of Control Release, Vol. 133, No. 2, 2009, pp. 132-138.
T. Musacchio, et al., “1H NMR Detection of Mobile Lipids as a Marker for Apoptosis: The Case of Anticancer Drug-Loaded Liposomes and Polymeric Micelles,” Molecular Pharmacetics, Vol. 6, No. 6, 2009, pp. 1876-1882.
A. Papagiannaros, et al., “Near Infrared Planar Tumor Imaging and quantification Using Nanosized Alexa 750-Labeled Phospholipid Micelles,” International Journal of Nanomedicine, Vol. 4, No. 1, 2009, pp. 123-131.
N. R. Patel, et al., “Mitochondria-Targeted Liposomes Improve the Apoptotic and Cytotoxic Action of Sclareol,” Journal of Liposome Research, Vol. 20, No. 3, 2010, pp. 244-249.
S. V. Boddapati, et al., “Organelle-Targeted Nanocarriers: Specific Delivery of Liposomal Ceramide to Mitochondria Enhances Its Cytotoxicity in vitro and in vivo,” Nano Letters, Vol. 8, No. 8, 2008, pp. 2559-2563.
A. Papagiannaros, et al., “Quantum Dots Encapsulated in Phospholipid Micelles for Imaging and Quantification of Tumors in the Near-Infrared Region,” Nanomedicine, Vol. 5, No. 2, 2009, pp. 216-224.
A. Papagiannaros, et al., “Quantum Dot Loaded Immunomicelles for Tumor Imaging,” BMC Medical Imaging, Vol. 10, 2010, 22 p.
J. F. Tomera and J. Martyn, “Systemic Effects Of Single Hindlimb Burn Injury on Skeletal Muscle Function and Cyclic Nucleotide Levels in the Murine Model,” Burns Including Thermal Injury, Vol. 14, No. 3, 1988, pp. 210-219.
J. Hennig, A. Nauerth and H. Friedburg, “RARE Imaging: A Fast Imaging Method for Clinical MR,” Magnetic Resonance in Medicine, Vol. 3, No. 6, 1986, pp. 823-833.
J. Frahm, A. Haase and D. Matthaei, “Rapid NMR Imaging of Dynamic Processes Using the FLASH Technique,” Magnetic Resonance in Medicine, Vol. 3, No. 2, 1986, pp. 321-327.
O. C. Andronesi, et al., “Combined off-Resonance Imaging and T2 Relaxation in the Rotating Frame for Positive Contrast MR Imaging of Iinfection in a Murine Burn Model,” Journal of Magnetic Resonance Imaging, Vol. 32, No. 5, 2010, pp. 1172-1183.
R. Waki, et al., “Development of a System to Sensitively and Specifically Visualize C-Fos mRNA in Living Cells Using Bispyrene-Modified RNA Probes,” Chemical Communications, Vol. 47, No. 14, 2011, pp. 4204-4206.
X. D. Zhang, et al., “Size-Dependent in vivo Toxicity of PEG-Coated Gold Nanoparticles,” International Journal of Nanomedicine, Vol. 6, No. 2011, pp. 2071-2081.
P. K. Liu, et al., “Transcription MRI: A New View of the Living Brain,” Neuroscientist, Vol. 14, No. 5, 2008, pp. 503-520.
C. H. Liu, et al., “Noninvasive Delivery of Gene Targeting Probes to Live Brains for Transcription MRI,” Official Publication of the Federation of American Societies for Experimental Biology, Vol. 22, No. 4, 2008, pp. 1193-1203.
R. R. Sawant, et al., “Polyethyleneimine-Lipid Conjugate-Based pH-Sensitive Micellar Carrier for Gene Delivery,” Biomaterials, Vol. 33, No. 15, 2012, pp. 39423951.
S. Movassaghian, et al., “Dendrosome-Dendriplex Inside Liposomes: As a Gene Delivery System,” Journal of Drug Targeting, Vol. 19, No. 10, 2012, pp. 925-932.
Y. T. Ko, et al., “Self-Assembling Micelle-Like Nanoparticles Based on Phospholipid-Polyethyleneimine Conjugates for Systemic Gene Delivery,” Journal of Controlled Release, Official Journal of the Controlled Release Society, Vol. 133, No. 2, 2009, pp. 132-138.
Y. T. Ko, et al., “Gene Delivery into Ischemic Myocardium by Double-Targeted Lipoplexes with Anti-Myosin Antibody and TAT Peptide,” Gene Therapy, Vol. 16, No. 1, 2009, pp. 52-59.