Hydrogel nanoparticles with covalently linked coomassie blue for brain tumor delineation visible to the surgeon.

Delineation of tumor margins is a critical and challenging objective during brain cancer surgery. A tumor-targeting deep-blue nanoparticle-based visible contrast agent is described, which, for the first time, offers in vivo tumor-specific visible color staining. This technology thus enables color-guided tumor resection in real time, with no need for extra equipment or special lighting conditions. The visual contrast agent consists of polyacrylamide nanoparticles covalently linked to Coomassie Blue molecules (for nonleachable blue color contrast), which are surface-conjugated with polyethylene glycol and F3 peptides for efficient in vivo circulation and tumor targeting, respectively.

[1]  S. Coons,et al.  Is gross-total resection sufficient treatment for posterior fossa ependymomas? , 2002, Journal of neurosurgery.

[2]  P. Willems,et al.  Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial. , 2006, Journal of neurosurgery.

[3]  M. Berger,et al.  GLIOMA EXTENT OF RESECTION AND ITS IMPACT ON PATIENT OUTCOME , 2008, Neurosurgery.

[4]  Moghimi,et al.  Subcutaneous and intravenous delivery of diagnostic agents to the lymphatic system: applications in lymphoscintigraphy and indirect lymphography. , 1999, Advanced drug delivery reviews.

[5]  M. Berger,et al.  Intracarotid RMP-7 Enhanced Indocyanine Green Staining of Tumors in a Rat Glioma Model , 2002, Journal of Neuro-Oncology.

[6]  Donghoon Lee,et al.  Optical and MRI multifunctional nanoprobe for targeting gliomas. , 2005, Nano letters.

[7]  Brian J. Tighe,et al.  Polymers for biodegradable medical devices. 1. The potential of polyesters as controlled macromolecular release systems , 1986 .

[8]  D. A. Hansen,et al.  Indocyanine green (ICG) staining and demarcation of tumor margins in a rat glioma model. , 1993, Surgical neurology.

[9]  D. A. Martinez,et al.  Assessment of disseminated pancreatic cancer: a comparison of traditional exploratory laparotomy and radioimmunoguided surgery. , 1997, Surgery.

[10]  C. Reichardt Solvents and Solvent Effects in Organic Chemistry , 1988 .

[11]  Oren Sagher,et al.  The Brain Tumor Window Model: A Combined Cranial Window and Implanted Glioma Model for Evaluating Intraoperative Contrast Agents , 2010, Neurosurgery.

[12]  Scott VandenBerg,et al.  Bromophenol Blue Staining of Tumors in a Rat Glioma Model , 2005, Neurosurgery.

[13]  Yasuhiko Kaku,et al.  Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note. , 2003, Journal of neurosurgery.

[14]  Yong-Eun Koo Lee,et al.  Near infrared luminescent oxygen nanosensors with nanoparticle matrix tailored sensitivity. , 2010, Analytical chemistry.

[15]  C. Nimsky,et al.  Intraoperative Magnetic Resonance Imaging Combined with Neuronavigation: A New Concept , 2001, Neurosurgery.

[16]  W. Hall,et al.  Does the extent of surgery have an impact on the survival of patients who receive postoperative radiation therapy for supratentorial low‐grade gliomas? , 2001, International journal of cancer.

[17]  R Weissleder,et al.  MR lymphography: study of a high-efficiency lymphotrophic agent. , 1994, Radiology.

[18]  H Stepp,et al.  Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. , 2000, Journal of neurosurgery.

[19]  H Stepp,et al.  Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. , 1998, Neurosurgery.

[20]  Ralph Weissleder,et al.  A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. , 2003, Cancer research.

[21]  S. Fujita A Convenient Preparation of Arenesulfonyl Chlorides from the Sodium Sulfonates and Phosphoryl Chloride/ Sulfolane , 1982 .

[22]  Miqin Zhang,et al.  Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier. , 2009, Cancer research.

[23]  D. Orringer,et al.  IN VITRO CHARACTERIZATION OF A TARGETED, DYE‐LOADED NANODEVICE FOR INTRAOPERATIVE TUMOR DELINEATION , 2009, Neurosurgery.

[24]  P. Beak,et al.  The endocyclic restriction test: the geometries of nucleophilic substitutions at sulfur(VI) and sulfur(II). , 2008, The Journal of organic chemistry.

[25]  Raoul Kopelman,et al.  Brain cancer diagnosis and therapy with nanoplatforms. , 2006, Advanced drug delivery reviews.

[26]  H. Chial,et al.  A spectral study of the charge forms of Coomassie blue G. , 1993, Analytical biochemistry.

[27]  S. Taylor,et al.  CLINICAL APPLICATIONS OF COOMASSIE BLUE , 1959, British heart journal.