일시: 2011년 4월 2일 오후 1:30
장소: 500동 404호

-Abstract-
Nanoscience has attracted attention as a fast burgeoning field with promising methodologies for the cancer diagnosis and therapy. Here, target specific nanoparticle-based platforms were designed to induce the apoptosis of human brain cancer cells and to show their capability for in vivo theragnostics which combines therapy and diagnosis.
Quantum Dot (QD)-based delivery system was demonstrated to deliver small interfering RNAs (siRNAs) and monitor its uptake using enhanced fluorescence properties of QDs as well as their high surface to volume ratio. siRNA-QDs against green fluorescent protein (GFP) not only showed increased efficiency of transfection and gene knockdown, but also synchronized QDs’ fluorescent color and their localization without further genetic analysis. As a model study, glioblastoma multiforme (GBM) was chosen because of high malignancy and invasiveness resulting in short mean survival rate, and necessity of advanced imaging probes for early diagnosis. Multiplexing with integrin-targeting RGD and TAT peptide enables siRNA-QDs to be delivered specifically to U87 cells, which are representative GBM cell line expressing high level of integrin. As a chemotheragnostic agent, target-specific siRNA-QDs were transfected into GBM cells that overexpress mutant epidermal growth factor receptor (EGFRvIII). Efficiently delivered siRNA-QDs against EGFRvIII led to abnormal cell morphology and decreased cell population caused by successful knockdown of EGFRvIII gene and resulting silencing of the PI3K/AKT signaling pathway which plays an important role in cancer cell proliferation and apoptosis. siRNA-QDs demonstrate that nanoparticle-based platform is an excellent and efficient multifunctional theragnostic agent for the clinical purpose.
In spite of high potential of siRNA-QD system, its cytotoxicity and skin depth issues lead to the development of a magnetic nanoparticle (MNP)-based theragnostic system for in vivo application. Graphite coated FeCo MNPs (FeCo/C) exhibited superparamagnetic properties with high crystallinity, magnetization, and T2- weighted magnetic resonance (MR) contrast. In addition, Raman imaging is allowed by graphite shell designed for protection of FeCo core from decomposition and oxidation. Compared to conventional iron oxide MNPs such as Resovist, FeCo/C showed much higher MR contrast both in vitro and in vivo, thus making it suitable for a diagnostic probe. Dextrans having different functional groups were also developed to stabilize FeCo/C in physiological condition as well as for conjugating therapeutic agents or targeting molecules such as siRNA, small molecule drugs, antibody, and cyclic RGD. High magnetization of FeCo/C allowed for target-specific hyperthermia against U87 cells to induce significant cell death by local heating induced under AC magnetic field. Additionally, using a combined approach, siRNA-FeCo/C against EGFRvIII followed by hyperthermia synergistically induced significant cell death of U87-EGFRvIII compared to individual treatments, which proved that the target-specific siRNA-FeCo/C system is a promising candidate of in vivo theragnostic agents.