Radiosensitization by Liposome-Encapsulated Fullerenes to Mitochondria/DNA-Damages on Human Melanoma Cells
Radiosensitization by Liposome-Encapsulated Fullerenes to Mitochondria/DNA-Damages on Human Melanoma Cells
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DOI：
10.1166/jnn.2018.15240
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发表时间：
2018-06-01
影响因子：
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通讯作者：
Miwa, Nobuhiko
中科院分区：
文献类型：
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作者：
Kato, Shinya;Yoshimura, Tetsuro;Miwa, Nobuhiko
将多羟基小间隙富勒烯[C120 O30（OH）（30）center dot 30 H（2）O center dot 25 Na（+）：SGF]包裹在由1，2-二油酰-sn-甘油-3-磷酸胆碱（DOPC）和1，2-二油酰-sn-甘油-3-磷酸胆碱（DOPS）组成的多层脂质体（Lpsm）中，命名为LpsmSGF（DOPC/DOPS/SGF = 35 mM：15 mM：246-445 μ M，直径= 141.2 nm，ζ-电位= -35.65 mV）。在人黑素瘤HMV-II细胞上评价了LpsmSGF在X射线照射下的放射增敏作用。X射线照射后第7天，WST-8评估的细胞增殖程度在Lpsm SGF预处理的细胞上比Lpsm或free-SGF更明显地降低。分别用罗丹明123、二氢乙锭或抗8-羟基脱氧鸟苷抗体对细胞进行荧光成像，作为细胞膜电位、细胞内超氧阴离子自由基（O-2-）或DNA氧化损伤的指示剂。X射线照射后，LpsmSGF的核周区线粒体膜电位明显高于Lpsm和free-SGF。没有X射线照射，超氧阴离子自由基被发现主要在细胞质中，但是，当暴露于X射线，他们被发现在细胞核与DNA氧化损伤与LpsmSGF预处理的细胞。同时，X射线辐照使SGF水溶液的氧化还原电位升高。这些结果表明，LpsmSGF介导的活性氧的产生导致细胞组分如线粒体和细胞上的DNA的损伤，从而细胞增殖降低。LpsmSGF具有作为促氧化型放射增敏剂的潜力。
The polyhydroxy small-gap fullerenes [C120O30(OH)(30) center dot 30H(2)O center dot 25Na(+): SGFs] were encapsulated in multilamellar liposomes (Lpsm) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine ( DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPS), which are designated as LpsmSGFs (DOPC/DOPS/SGFs = 35 mM: 15 mM: 246-445 mu M, diameter = 141.2 nm, zeta-potential = -35.65 mV). Radiosensitization by LpsmSGFs under X-ray irradiation was evaluated on human melanoma HMV-II cells. On 7th day after X-ray irradiation, cell proliferation degree assessed by WST-8 decreased more markedly on cells pretreated with LpsmSGFs than Lpsm or free-SGFs. Fluorescent imaging of cells with Rhodamine123, dihydroethidium or anti-8-hydroxydeoxyguanosine antibody was monitored as an indicator for mitochondrialmembrane potentials, intracellular superoxide anion radicals (O-2-) or oxidative DNA-damages, respectively. After X-ray irradiation, LpsmSGFs obviously exhibited more augmented mitochondrial membrane potentials on perinuclear region of cells than Lpsm or free-SGFs. Without X-ray irradiation, superoxide anion radicals were found principally in the cytoplasm, but, when exposed to X-ray, they were found in cell nuclei associated with oxidative DNA-damages on cells pretreated with LpsmSGFs. Meanwhile, the oxidation-reduction potentials of SGFs aqueous solution increased by X-ray irradiation. These results suggest that LpsmSGFs-mediated generation of reactive oxygen species results in damages to cellular components such as mitochondria and DNA on cells, and thereby cell proliferation decreased. The LpsmSGFs has a potential as a pro-oxidative type radiosensitizer.