Dahlstedt Emma, Collins Hazel A, Balaz Milan, Kuimova Marina K, Khurana Mamta, Wilson Brian C, Phillips David, Anderson Harry L
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX13TA, UK.
Org Biomol Chem. 2009 Mar 7;7(5):897-904. doi: 10.1039/b814792b. Epub 2009 Jan 9.
Two-photon excited photodynamic therapy (PDT) has the potential to provide a highly targeted treatment for neoplastic diseases, as excitation can be pin-pointed to small volumes at the laser focus. In addition, two-photon PDT offers deeper penetration into mammalian tissue due to the longer wavelength of irradiation. Here we report the one-photon and two-photon excited PDT results for a collection of conjugated porphyrin dimers with high two-photon absorption cross sections. These dimers demonstrate high one-photon PDT efficacy against a human ovarian adenocarcinoma cell line (SK-OV-3) and exhibit no significant dark-toxicity at concentrations of up to 20 microM. Their one-photon excited PDT efficiencies, following irradiation at 657 nm, approach that of Visudyne, a drug used clinically for PDT. We investigated and optimised the effect of the photosensitizer concentration, incubation time and the light dose on the PDT efficacy of these dimers. These studies led to the selection of P2C2-NMeI as the most effective porphyrin dimer. We have demonstrated that P2C2-NMeI undergoes a two-photon activated process following excitation at 920 nm (3.6-6.8 mW, 300 fs, 90 MHz) and compared it to Visudyne. We conclude that the in vitro two-photon PDT efficacy of P2C2-NMeI is about twice that of Visudyne. This result highlights the potential of this series of porphyrin dimers for two-photon PDT.
双光子激发光动力疗法（PDT）有潜力为肿瘤疾病提供高度靶向治疗，因为激发可精确指向激光焦点处的小体积区域。此外，由于照射波长更长，双光子PDT能更深地穿透哺乳动物组织。在此，我们报告了一系列具有高双光子吸收截面的共轭卟啉二聚体的单光子和双光子激发PDT结果。这些二聚体对人卵巢腺癌细胞系（SK-OV-3）显示出高单光子PDT疗效，并且在浓度高达20微摩尔时无明显暗毒性。在657纳米照射后，它们的单光子激发PDT效率接近维速达尔（一种临床上用于PDT的药物）。我们研究并优化了光敏剂浓度、孵育时间和光剂量对这些二聚体PDT疗效的影响。这些研究促使我们选择P2C2-NMeI作为最有效的卟啉二聚体。我们已证明，P2C2-NMeI在920纳米（3.6 - 6.8毫瓦，300飞秒，90兆赫）激发后经历双光子激活过程，并将其与维速达尔进行了比较。我们得出结论，P2C2-NMeI的体外双光子PDT疗效约为维速达尔的两倍。这一结果凸显了这一系列卟啉二聚体用于双光子PDT的潜力。
