Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform

被引:26
作者
Kazmi, Farasat [1 ,7 ]
Vallis, Katherine A. [2 ]
Vellayappan, Balamurugan A. [3 ]
Bandla, Aishwarya [4 ]
Yukun, Duan [5 ]
Carlisle, Robert [6 ]
机构
[1] Univ Oxford, Dept Oncol, Early Phase Clin Trials Unit, Oxford OX3 7LE, England
[2] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford OX3 7LE, England
[3] Natl Univ Canc Inst NCIS, Dept Radiat Oncol, Singapore 119228, Singapore
[4] NUS, Singapore Inst Neurotechnol SINAPSE, Singapore 117456, Singapore
[5] NUS, Dept Chem & Biomol Engn, Singapore 117456, Singapore
[6] Univ Oxford, Dept Biomed Engn, Oxford OX3 7DQ, England
[7] Univ Oxford, Churchill Hosp, Dept Oncol, Early Phase Clin Trials Unit, Oxford OX3 7LE, England
基金
英国工程与自然科学研究理事会;
关键词
nanoparticles; glioblastoma multiform; radiosensitizers; external beam radiotherapy; X-RAYS; SIZE; CYTOTOXICITY; RADIOTHERAPY; ENHANCEMENT;
D O I
10.3390/ijms21020429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gold nanoparticles (GNPs) have demonstrated significant dose enhancement with kilovoltage (kV) X-rays; however, recent studies have shown inconsistent findings with megavoltage (MV) X-rays. We propose to evaluate the radiosensitization effect on U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization were measured using MTS and clonogenic cellular radiation sensitivity assays, respectively. The sensitization enhancement ratio was calculated for 2 Gy (SER2Gy) with GNP (100 mu g/mL). Dark field and MTS assays revealed high co-localization and good biocompatibility of the GNPs with GBM cells. A significant sensitization enhancement of 1.45 (p = 0.001) was observed with GNP 100 mu g/mL. Similarly, at 6 Gy, there was significant difference in the survival fraction between the GBM alone group (mean (M) = 0.26, standard deviation (SD) = 0.008) and the GBM plus GNP group (M = 0.07, SD = 0.05, p = 0.03). GNPs enabled radiosensitization in U87 GBM cells at 2 Gy when irradiated using a clinical platform. In addition to the potential clinical utility of GNPs, these studies demonstrate the effectiveness of a robust and easy to standardize an in-vitro model that can be employed for future studies involving metal nanoparticle plus irradiation.
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页数:12
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