산화철 나노입자의 U373MG 세포 독성평가 및 방사선 세포생존 곡선에 미치는 영향에 대한 연구 = A Research on Superparamagnetic Iron Oxide Nanoparticles’ Toxicity to U373MG Cell and its Effect on the Radiation Survival Curve

국문 초록 (Abstract)

본 연구는 초상자성 산화철 나노입자 (SPIONs)의 세포독성평가 및 SPIONs를 uptake한 뇌신경교종 (glioblastoma multiforme, GBM) 세포의 방사선 세포생존곡선을 구하기 위해 수행되었으며, 본 연구의 결과는 양성자선과 SPIONs 이용한 GBM의 양성자선 치료선량 정보 등 양성자선 치료효과를 개선하기 위한 기초자료로 활용될 수 있을 것이다. SPIONs의 세포독성을 평가는 in vitro 실험 후 MTT 분석법을 이용하여 수행하였다. 독성평가 결과 1~100㎍/ml의 농도에서는 세포생존율의 유의한 차이가 나타나지 않았다. 하지만 200㎍/ml의 농도에서는 세포생존율이 74.2%로 감소 하며 세포독성을 나타냈다. SPIONs가 uptake 된 U373MG세포와 uptake 되지 않은 U373MG세포에 0~5 Gy의 양성자선을 조사하여 각각에 대한 세포생존곡선을 측정한 결과를 분석하여 SPIONs가 uptake된 U373MG세포의 세포생존율이 더 급격히 감소함을 알 수 있었다. 결론적으로 SPIONs가 uptake 된 세포에서는 보다 적은 선량으로도 세포사멸을 유도할 수 있음을 알 수 있었다. 따라서 GBM에 SPIONs를 타겟팅하면 양성자선을 이용한 뇌신경교종 치료효과를 개선할 수 있음을 보였다.

다국어 초록 (Multilingual Abstract)

This research was performed to evaluate the superparamagnetic iron oxide nanoparticles’(SPIONs) cell toxicity and to measure the radiation cell survival curve changes of SPIONs-uptake glioblastoma multiforme cells. The results could be practically used as the fundamental data to ameliorate proton beam cancer therapy, for example, providing necessary GBM treatment dose in the proton beam therapy when the therapy takes advantage of SPIONs. The assessment of the toxicological evaluation of synthesized SPIONs was accomplished by MTT assay as an in vitro experiment. The results showed no meaningful differences in the cell survival rate at the 1-100㎍/ml SPIONs concentrations, but the cell toxicity was shown as the cell survival rate decreased up to 74.2% at the 200㎍/ml SPIONs concentration. Then, we measured each radiation cell survival curve for U373MG cells and SPIONs-uptake U373MG cells with 0~5 Gy of proton beam irradiations. It is learned from the analysis of the experimental results that the SPION-uptake cells’ radiation survival rate was more rapidly decreased as the irradiation dose increased. In conclusion we confirmed that SPIONs-uptake in U373MG cells induces cell death at the much less dose than the lethal dose of SPION-non-uptake cell. This research shows that the therapeutic efficacy of glioblastoma multiforme treatment in proton beam therapy can be improved by SPIONs targeting to the GBM cells.

목차 (Table of Contents)

• Abstract
• 요약
• Ⅰ. 서론
• Ⅱ. 재료 및 방법
• Ⅲ. 결과
• Ⅳ. 고찰
• Ⅴ. 결론
• 참고문헌

참고문헌 (Reference)

1 W.Rueter, 46 : 3194-, 1975

2 김대용, "특집/양성자치료" 대한의사협회 51 (51): 638-642, 2008

3 "http://mc50.kirams.re.kr"

4 Jong-Ki Kim, "Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect" IOP PUBLISHING LTD 21 : 2010

5 Barbara Alicja jereczek-Fossa, "Particle beam radiotherapy for head and neck tumors: Radiobiological basis and clinical experience" 28 : 750-760, 2006

6 KM Prise, "New insights on cell death from radiation exposure" 6 : 520-528, 2005

7 Xuan Phuc Nguyen, "Iron oxide-based conjugates for cancer theragnostics" 3 : 13-, 2012

8 Van Meir, E. G, "Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma" 60 (60): 166-193, 2010

9 Berridge MV, "Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction" 303 : 474-482, 1993

10 Paola Scampoli, "Biological effects of accelerated protons" 73 : 130-133, 2004

11 JM Hillegass, "Assessing nanotoxicity in cells in vitro" 2 : 219-231, 2010