Effects of photoacoustic imaging and photothermal ablation therapy mediated by targeted hollow gold nanospheres in an orthotopic mouse xenograft model of glioma.

Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7°C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results show the feasibility of using a single nanostructure for image-guided local tumor PTA therapy with photoacoustic molecular imaging.

[1]  Chenjie Xu,et al.  PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles , 2008, Journal of Nuclear Medicine.

[2]  G. Christofori.  Snail1 links transcriptional control with epigenetic regulation , 2010, The EMBO journal.

[3]  P. Lieberman,et al.  Molecular and Cellular Pathobiology Cancer Research 14-3-3 Binding Sites in the Snail Protein Are Essential for Snail-Mediated Transcriptional Repression and Epithelial-Mesenchymal Differentiation , 2010 .

[4]  Masahiro Inoue,et al.  Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. , 2009, Cancer cell.

[5]  D. Branstetter,et al.  RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis , 2010, Nature.

[6]  G. Christofori,et al.  Angiopoietin-1 and -2 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis. , 2011, Cancer research.

[7]  Simone Brabletz,et al.  The ZEB1/miR‐200 feedback loop controls Notch signalling in cancer cells , 2011, The EMBO journal.

[8]  W. Dewey,et al.  Thermal dose determination in cancer therapy. , 1984, International journal of radiation oncology, biology, physics.

[9]  G. Capellá,et al.  Filamin B Plays a Key Role in Vascular Endothelial Growth Factor-induced Endothelial Cell Motility through Its Interaction with Rac-1 and Vav-2* , 2010, The Journal of Biological Chemistry.

[10]  Da-Qiang Li,et al.  Bidirectional autoregulatory mechanism of metastasis-associated protein 1-alternative reading frame pathway in oncogenesis , 2011, Proceedings of the National Academy of Sciences.

[11]  Horst Kessler,et al.  Radiolabeled αvβ3 Integrin Antagonists: A New Class of Tracers for Tumor Targeting , 1999 .

[12]  C. Marshall,et al.  The plasticity of cytoskeletal dynamics underlying neoplastic cell migration. , 2010, Current opinion in cell biology.

[13]  K. Alitalo,et al.  Effective suppression of vascular network formation by combination of antibodies blocking VEGFR ligand binding and receptor dimerization. , 2010, Cancer cell.

[14]  Kedar S Vaidya,et al.  Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. , 2007, Journal of the National Cancer Institute.

[15]  T. Mikkelsen,et al.  Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  T. Brabletz,et al.  A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells , 2008, EMBO reports.

[17]  Thomas Lengauer,et al.  A DNA methylation fingerprint of 1 , 628 human samples Material , 2011 .

[18]  R. Adams,et al.  Dynamics of endothelial cell behavior in sprouting angiogenesis. , 2010, Current opinion in cell biology.

[19]  Dimos Baltas,et al.  CT-Guided Interstitial HDR Brachytherapy for Recurrent Glioblastoma Multiforme , 2007, Strahlentherapie und Onkologie.

[20]  S. Emelianov,et al.  Photoacoustic imaging and temperature measurement for photothermal cancer therapy. , 2008, Journal of biomedical optics.

[21]  J. Joyce,et al.  IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. , 2010, Genes & development.

[22]  Younan Xia,et al.  Gold nanocages as photothermal transducers for cancer treatment. , 2010, Small.

[23]  V. Zharov,et al.  Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. , 2009, Nature nanotechnology.

[24]  Nastassja A. Lewinski,et al.  Nanoshell-mediated photothermal therapy improves survival in a murine glioma model , 2011, Journal of Neuro-Oncology.

[25]  C. Klein,et al.  Parallel progression of primary tumours and metastases , 2009, Nature Reviews Cancer.

[26]  P. Wust,et al.  Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme , 2010, Journal of Neuro-Oncology.

[27]  Wei Wang,et al.  Probing for Integrin αvβ3 Binding of RGD Peptides Using Fluorescence Polarization , 2005 .

[28]  M Schwaiger,et al.  Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  Zhuang Liu,et al.  Carbon nanotubes as photoacoustic molecular imaging agents in living mice. , 2008, Nature nanotechnology.

[30]  K. Alitalo,et al.  Lymphangiogenesis: Molecular Mechanisms and Future Promise , 2010, Cell.

[31]  Wei Lu,et al.  Targeted Photothermal Ablation of Murine Melanomas with Melanocyte-Stimulating Hormone Analog–Conjugated Hollow Gold Nanospheres , 2009, Clinical Cancer Research.

[32]  Wei Lu,et al.  Tumor Site–Specific Silencing ofNF-κB p65by Targeted Hollow Gold Nanosphere–Mediated Photothermal Transfection , 2010, Cancer Research.

[33]  F. Orsenigo,et al.  Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5 , 2008, Nature Cell Biology.

[34]  Lihong V. Wang,et al.  Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain , 2003, Nature Biotechnology.

[35]  Wei Lu,et al.  Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres. , 2010, Biomaterials.

[36]  Michael J Sailor,et al.  Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. , 2009, Cancer research.

[37]  R. Kerbel,et al.  Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens , 2009, Clinical Cancer Research.

[38]  Wenjun Guo,et al.  The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells , 2008, Cell.

[39]  E. Novellino,et al.  Imaging of αvβ3 Expression by a Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5 , 2009, Clinical Cancer Research.

[40]  M. Esteller,et al.  Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome , 2011, Epigenetics.

[41]  R. Kalluri,et al.  Methylation determines fibroblast activation and fibrogenesis in the kidney , 2010, Nature Medicine.

[42]  M. Schwaiger,et al.  Radiolabeled alpha(v)beta3 integrin antagonists: a new class of tracers for tumor targeting. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[43]  H. Gerhardt,et al.  Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting , 2010, Nature Cell Biology.

[44]  J. BotellaLlusiá,et al.  [Long-term results]. , 1983, Anales de la Real Academia Nacional de Medicina.

[45]  Peter Wust,et al.  Intracranial Thermotherapy using Magnetic Nanoparticles Combined with External Beam Radiotherapy: Results of a Feasibility Study on Patients with Glioblastoma Multiforme , 2006, Journal of Neuro-Oncology.