X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield.
X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield.
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DOI：
10.1038/srep19954
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发表时间：
2016-01-28
影响因子：
4.6
通讯作者：
Goldys EM
中科院分区：
文献类型：
--
作者：
Clement S;Deng W;Camilleri E;Wilson BC;Goldys EM
单线态氧是光动力疗法中主要的细胞毒剂。我们发现，在紫外光和8 keV X射线照射下，纯的CeF3纳米粒子以及与光敏剂维替普芬通过静电作用而结合的CeF3纳米粒子能够产生单线态氧。经X射线激发的单线态氧量子产率为0.79 ±CeF_3，为最高偶联水平，每粒CeF_3中含有31个维替普芬分子。根据这一结果，我们估算了治疗剂量为60 Gy6 MeV和30 keV的电离辐射所产生的单线态氧分子分别为(1.2 ± 0.7) × 10 8和(2.0 ± 0.1) × 10 9。这与文献中报道的光动力疗法中每个细胞5 × 107-2 × 109单线态氧分子的细胞毒性剂量相当。我们证实CeF_3-VP偶联物增强了6 MeV辐射对细胞的杀伤作用。这项工作证实了使用X射线或γ激活的纳米粒子-光敏剂偶联物的可行性，无论是作为癌症放射治疗的补充，还是作为一种独立的治疗方式。
Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 ± 0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF3-verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 ± 0.7) × 108 and (2.0 ± 0.1) × 109 singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 × 107–2 × 109 singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or γ- ray activated nanoparticle-photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality.