Showing papers by "Jerry S.H. Lee published in 2008"

Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles.

Abstract: Nanoparticles have been investigated as drug delivery vehicles, contrast agents, and multifunctional devices for patient care. Current nanoparticle-based therapeutic strategies for cancer treatment have been mainly based on delivery of chemotherapeutic agents to induce apoptosis or DNA/siRNA to regulate oncogene expression. Here, we present a nanoparticle system that demonstrates an alternative approach to the treatment of cancers, through the inhibition of cell invasion, while serving as a magnetic resonance and optical imaging contrast agent. The nanoparticle is comprised of an iron oxide nanoparticle core, conjugated with an amine-functionalized PEG silane and a small peptide, chlorotoxin (CTX), which enables the tumor cell-specific binding of the nanoparticle. We show that the nanoparticle exhibits substantially enhanced cellular uptake and an invasion inhibition rate of ~98% compared to unbound CTX (~45%). Significantly, our investigation from flow cytometry analysis, transmission electron microscopy and fluorescent imaging revealed that the CTX-enabled nanoparticles deactivated the membrane-bound matrix metalloproteinase 2 (MMP-2) and induced increased internalization of lipid rafts that contain surface-expressed MMP-2 and volume-regulating ion channels through receptor-mediated endocytosis, leading to enhanced prohibitory effects. Since upregulation and activity of MMP-2 have been observed in tumors of neuroectodermal origin, and in cancers of the breast, colon, skin, lung, prostate, ovaries and a host of others, this nanoparticle system can be potentially used for non-invasive diagnosis and treatment of a variety of cancer types.

Next Generation Nanosolutions for Cancer Treatment and Diagnosis

Abstract: This review describes several state of the art advances made in the field of cancer nanotechnology that bring the science closer to clinical realization for application in disease treatment and diagnosis. For therapeutic delivery, in vivo strategies to improve the biodistribution, tumor penetration, and cellular uptake of nanocarriers are discussed, including the precise control of formulation and conjugation of targeting agents. We highlight recently developed novel nanosolutions that specifically address cancer metastasis. We also describe in detail the promising use of nanotechnologies for in vitro diagnostics on tissue section samples, an area that appears to be ready for clinical application in the near future. Finally, we discuss emerging discoveries on the unique biophysical properties of cancer that hold promise for paradigm shifts in future cancer diagnosis and treatment strategies as this field continues to mature. (Cancer & Chemotherapy