Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan ROC.
Small. 2014 Apr 24;10(8):1612-22. doi: 10.1002/smll.201302719. Epub 2013 Dec 16.
Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1-48 W/cm²) irradiation, leading to hyperthermia-induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs-mediated PTT and organic photosensitizers-mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs-mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti-cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon-induced fluorescence to illustrate their in vivo locations/distribution.
先前有大量文献报道,金纳米棒(Au NRs)在高激光剂量(通常为 808nm、1-48W/cm²)照射下能有效杀死癌细胞,导致癌细胞因热疗而被破坏,即光热治疗(PTT)效应。也有报道称,Au NRs 介导的 PTT 与有机光敏剂介导的光动力疗法(PDT)相结合,可实现协同的 PTT 和 PDT 效应,从而杀死癌细胞。在此,我们首次证明,Au NRs 本身可以敏化单线态氧(¹O₂)的形成,并在非常低的单光子近红外(915nm,<130mW/cm²)光激发下的 LED/激光剂量下,对小鼠肿瘤的完全破坏发挥显著的 PDT 效应。通过改变近红外光激发波长,可以将 Au NRs 介导的光疗效应从 PDT 切换为 PTT 或两者的组合。通过细胞实验中活性氧(ROS)和热休克蛋白(HSP70)、单线态氧传感器绿(SOSG)检测和叠氮化钠淬灭的测量,证实了 PDT 和 PTT 效应。体内小鼠实验进一步表明,通过 915nm 照射 Au NRs 的 PDT 效应能比阿霉素(一种临床使用的抗癌药物)以及通过 780nm 光照射 Au NRs 的 PTT 效应更有效地破坏小鼠的 B16F0 黑色素瘤肿瘤。此外,我们还证明 Au NRs 可以发出单光子诱导的荧光,以说明其在体内的位置/分布。