Department of Nuclear Medicine and Radiobiology and Medical Research Center, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Department of Radiological Technology and Medical Physics, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Mol Sci. 2020 Jul 9;21(14):4848. doi: 10.3390/ijms21144848.
A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery. Radiosensitization by GNPs alone or carboplatin alone was observed only at high concentrations of these compounds. Furthermore, low doses of carboplatin alone or a combination of carboplatin and GNPs did not engender radiosensitization. However, the same low doses of carboplatin and GNPs administered simultaneously by encapsulation in liposomal nanocarriers (LipoGold) led to radiosensitization and efficient control of cell proliferation. Our study shows that the radiosensitizing effect of a combination of carboplatin and GNPs is remarkably more efficient when both compounds are simultaneously delivered to the tumor cells using a liposomal carrier.
采用交错人字形微流控方法制备了金纳米颗粒(GNPs)和卡铂的脂质体制剂,命名为 LipoGold。在体外,用人结直肠癌细胞系 HCT116 的集落形成试验评估了 LipoGold 以及类似浓度的非脂质体 GNPs、卡铂和奥沙利铂的放射增敏作用。在接受 10Gy 照射后,通过对流增强递送将 LipoGold、GNPs 或卡铂直接注入皮下植入的 HCT116 肿瘤中,监测 NU/NU 小鼠中 HCT116 肿瘤的进展。仅在这些化合物的高浓度下观察到 GNPs 或卡铂单独的放射增敏作用。此外,单独使用低剂量卡铂或卡铂和 GNPs 的组合并未引起放射增敏作用。然而,同时通过脂质体纳米载体(LipoGold)包封给予相同的低剂量卡铂和 GNPs 导致了放射增敏作用和对细胞增殖的有效控制。我们的研究表明,当使用脂质体载体同时将两种化合物递送至肿瘤细胞时,卡铂和 GNPs 的组合的放射增敏作用显著更有效。