Vascular-targeted photothermal therapy of an orthotopic murine glioma model.

AIM To develop nanoshells for vascular-targeted photothermal therapy of glioma. MATERIALS & METHODS The ability of nanoshells conjugated to VEGF and/or poly(ethylene glycol) (PEG) to thermally ablate VEGF receptor-2-positive endothelial cells upon near-infrared laser irradiation was evaluated in vitro. Subsequent in vivo studies evaluated therapy in mice bearing intracerebral glioma tumors by exposing tumors to near-infrared light after systemically delivering saline, PEG-coated nanoshells, or VEGF-coated nanoshells. The treatment effect was monitored with intravital microscopy and histology. RESULTS VEGF-coated but not PEG-coated nanoshells bound VEGF receptor-2-positive cells in vitro to enable targeted photothermal ablation. In vivo, VEGF targeting doubled the proportion of nanoshells bound to tumor vessels and vasculature was disrupted following laser exposure. Vessels were not disrupted in mice that received saline. The normal brain was unharmed in all treatment and control mice. CONCLUSION Nanoshell therapy can induce vascular disruption in glioma.

[1]  J. Folkman.  Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[2]  Raoul Kopelman,et al.  Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors , 2006, Clinical Cancer Research.

[3]  W. Dahut,et al.  Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[4]  Xiaohua Huang,et al.  Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles. , 2006, Cancer letters.

[5]  Naomi J Halas,et al.  Immunonanoshells for targeted photothermal ablation of tumor cells , 2006, International journal of nanomedicine.

[6]  S. Nie,et al.  A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands. , 2010, ACS nano.

[7]  Wei Lu,et al.  Copper sulfide nanoparticles for photothermal ablation of tumor cells. , 2010, Nanomedicine.

[8]  Naomi J. Halas,et al.  Nanoengineering of optical resonances , 1998 .

[9]  S. Choudhury,et al.  Role of Angiogenesis in the Pathogenesis of Glioblastoma and Antiangiogenic Therapies for Controlling Glioblastoma , 2010 .

[10]  K. Plate,et al.  Vascular endothelial growth factor and glioma angiogenesis: Coordinate induction of VEGF receptors, distribution of VEGF protein and possible In vivo regulatory mechanisms , 1994, International journal of cancer.

[11]  R. Gilbertson,et al.  Regression of experimental medulloblastoma following transfer of HER2-specific T cells. , 2007, Cancer research.

[12]  P. Vajkoczy,et al.  Angiogenesis in malignant glioma--a target for antitumor therapy? , 2006, Critical reviews in oncology/hematology.

[13]  Hui Zhang,et al.  Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. , 2007, Nano letters.

[14]  Glioblastoma multiforme: an emerging paradigm of anti-VEGF therapy. , 2008, Expert opinion on biological therapy.

[15]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. West,et al.  Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer , 2010, International journal of nanomedicine.

[17]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[18]  Weihong Tan,et al.  Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[19]  T. Taxt,et al.  Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma , 2011, Proceedings of the National Academy of Sciences.

[20]  Feng Gao,et al.  RGD-conjugated dendrimer-modified gold nanorods for in vivo tumor targeting and photothermal therapy. , 2010, Molecular pharmaceutics.

[21]  M. Chamberlain.  Antiangiogenesis: biology and utility in the treatment of gliomas , 2008, Expert review of neurotherapeutics.

[22]  Nastassja A. Lewinski,et al.  A new era for cancer treatment: gold-nanoparticle-mediated thermal therapies. , 2011, Small.

[23]  Yi Li,et al.  Immunoconjugated gold nanoshell-mediated photothermal ablation of trastuzumab-resistant breast cancer cells , 2010, Breast Cancer Research and Treatment.

[24]  J. West,et al.  Near-infrared-resonant gold/gold sulfide nanoparticles as a photothermal cancer therapeutic agent. , 2010, Small.

[25]  S. Niclou,et al.  Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms , 2009, Expert opinion on therapeutic targets.

[26]  Xiaohua Huang,et al.  Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. , 2006, Journal of the American Chemical Society.

[27]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[28]  J. Bartek,et al.  Autocrine regulation of glioblastoma cell-cycle progression, viability and radioresistance through the VEGF-VEGFR2 (KDR) interplay , 2008, Cell cycle.

[29]  Glenn P. Goodrich,et al.  Photothermal Efficiencies of Nanoshells and Nanorods for Clinical Therapeutic Applications , 2009 .

[30]  Jennifer L West,et al.  Nanoparticles for thermal cancer therapy. , 2009, Journal of biomechanical engineering.

[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]  Milan Makale,et al.  Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis , 2008, Proceedings of the National Academy of Sciences.

[33]  Mark E. Davis,et al.  Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[34]  T. Merchant,et al.  An intravital microscopy study of radiation-induced changes in permeability and leukocyte-endothelial cell interactions in the microvessels of the rat pia mater and cremaster muscle. , 2004, Brain research. Brain research protocols.

[35]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[36]  Erik C. Dreaden,et al.  Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice. , 2008, Cancer letters.

[37]  Takuro Niidome,et al.  PEG-modified gold nanorods with a stealth character for in vivo applications. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Xingde Li,et al.  A quantitative study on the photothermal effect of immuno gold nanocages targeted to breast cancer cells. , 2008, ACS nano.

[39]  Dong Liang,et al.  A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy. , 2010, Journal of the American Chemical Society.

[40]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[41]  Peter Vajkoczy,et al.  Combined inhibition of VEGF‐ and PDGF‐signaling enforces tumor vessel regression by interfering with pericyte‐mediated endothelial cell survival mechanisms , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  R Jason Stafford,et al.  Feasibility study of particle-assisted laser ablation of brain tumors in orthotopic canine model. , 2009, Cancer research.

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