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X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy : determination of singlet oxygen quantum yield

机译:纳米粒子-光敏剂偶联物在X射线诱导下的光动力疗法产生单线态氧的产生:单线态氧量子产率的测定

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摘要

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.
机译:单线态氧是光动力疗法中的主要细胞毒剂。我们表明,CeF 3纳米粒子,由于其纯净以及通过与光敏剂Verteporfin的静电相互作用而共轭,能够通过紫外线和8 keV X射线辐照产生单线态氧。对于每个CeF 3纳米粒子具有31个Verteporfin分子的结合物,经X射线激发的单线态氧量子产率确定为0.79±0.05,这是所用的最高结合水平。根据此结果,我们估计在剂量为6 MeV和30 keV的60 Gy电离辐射下,CeF₃-verteporfin共轭物产生的单线态氧剂量为(1.2±0.7)×10⁸和(2.0±0.1)×10⁹每个细胞的单线态氧分子。这些与文献中报道的使用光激活进行光动力疗法的每细胞5×10 –2×10⁹单线态氧分子的细胞毒性剂量相当。我们证实,CeF 3 -VP结合物增强了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射线活化的纳米粒子-光敏剂结合物来补充癌症的放射治疗或作为独立治疗手段的可行性。

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