A multifunctional nanoprobe capable of targeting glioma cells, detectable by both magnetic resonance imaging and fluorescence microscopy, was developed. The nanoprobe was synthesized by coating iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG) polymer, which were subsequently functionalized with chlorotoxin and the near-infrared fluorescing molecule Cy5.5. Both MR imaging and fluorescence microscopy showed significant preferential uptake of the nanoparticle conjugates by glioma cells. Such a nanoprobe could potentially be used to image resections of glioma brain tumors in real time and to correlate preoperative diagnostic images with intraoperative pathology at cellular-level resolution.

Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies. [Cancer Res 2007;67(14):6882-8]

Chemokines play a vital role in tumor progression and metastasis. Chemokines are involved in the growth of many cancers including breast cancer, ovarian cancer, pancreatic cancer, melanoma, lung cancer, gastric cancer, acute lymphoblastic leukemia, colon cancer, non-small lung cancer and non-hodgkin's lymphoma among many others. The expression of chemokines and their receptors is altered in many malignancies and leads to aberrant chemokine receptor signaling. This review focuses on the role of chemokines in key processes that facilitate tumor progression including proliferation, senescence, angiogenesis, epithelial mesenchymal transition, immune evasion and metastasis.

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