七种光引发剂引发的聚合物在不同组织细胞中的细胞毒性和细胞相容性比较,Toxicology in Vitro

光引发剂（PIs）在工业领域广泛用于光聚合，最近在生物医学领域受到密切关注。然而，关于它们对人类健康的毒性的报道很少。在这里，我们探索了七种商业和工业用 PI 的细胞毒性和细胞相容性，以开发其潜在的临床应用。苯基双（酰基）氧化膦 (BAPO)、2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone (369)、4,4'-Bis(diethylamino) 二苯甲酮 (EMK)、二苯基 (2,4,6-三甲基苯甲酰基）氧化膦（TPO）和2-异丙基噻吨酮（ITX）在1～50 μM浓度下对四种组织类型的细胞在非辐照条件下产生不同程度的细胞毒性，其中BAPO的细胞毒性最高，而乙基（2,4，6-三甲基苯甲酰基）苯基次膦酸盐（TPOL）和苯甲酰基甲酸甲酯（MBF）的细胞毒性最低。细胞系和原代细胞似乎对 BAPO 毒性高度敏感，原代淋巴细胞对光引发剂 369 (369) 和 EMK 毒性，LO2 细胞对 EMK 和 TPO 毒性，原代淋巴细胞和 HUVEC-12 细胞对 MBF 毒性，但只有 HEK293T细胞对369没有毒性。此外，这些PIs在暴露于455 nm蓝光后导致细胞毒性不同程度地增加，这与非辐照趋势一致。所有细胞对 TPOL 和 MBF 均表现出低敏感性，其中 TPOL 引发的聚合物对 MBF 的细胞相容性显着优于临床专用樟脑醌 (CQ)。新发现表明，BAPO 是七种 PI 中毒性最大的，但 TPOL 和 MBF 毒性最小，指导它们的开发和应用。结合其引发的聚合物细胞相容性和颜色以及报道的深度固化效率，TPOL 更有希望应用于临床实践。

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Photoinitiators (PIs) are widely used for photopolymerization in industrial area and recently paid close attention to in biomedical field. However, there are few reports on their toxicity to human health. Here we explored cytotoxicity and cytocompatibilty of seven commercial and industrial-used PIs for developing their potential clinical application. Phenylbis(acyl) phosphine oxides (BAPO), 2-Benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone (369), 4,4’-Bis(diethylamino) benzophenone (EMK), Diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), and 2-Isopropylthioxanthone (ITX) caused different extent cytotoxicities to four tissue types of cells at the concentrations of 1 to 50 μM under a non-irradiation condition, of which the BAPO cytotoxicity was the highest, whereas Ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPOL) and Methyl benzoylformate (MBF) displayed the lowest cellular toxicity. The cell lines and primary cells appeared highly sensitive to BAPO toxicity, the primary lymphocytes relatively to photoinitiator 369 (369) and EMK toxicities, LO2 cells to EMK and TPO toxicities, the primary lymphocytes and HUVEC-12 cells to MBF toxicity, but only HEK293T cells not to 369 toxicity. Furthermore, these PIs led to increasing cytotoxicity to different extents after exposure to 455 nm blue light, which is consistent with non-irradiation tendency. All the cells presented low sensitivity to TPOL and MBF, of which TPOL-triggered polymer is dramatically superior in its cytocompatibility to MBF, and in its transparency to clinically exclusively-used camphorquinone (CQ). The novel findings indicate that BAPO is the most toxic among the seven PIs, but TPOL and MBF are the least toxic, directing their development and application. Combined their triggered polymer cytocompatibility and color with reported deep curing efficiency, TPOL is more promising to be applied especially to clinical practice.