Department of Bioengineering, Faculty of Engineering, National University of Singapore, Singapore.
Nat Med. 2012 Oct;18(10):1580-5. doi: 10.1038/nm.2933. Epub 2012 Sep 16.
Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica-coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual-photosensitizer approach compared to approaches using a single photosensitizer, as determined by enhanced generation of singlet oxygen and reduced cell viability. In vivo studies also showed tumor growth inhibition in PDT-treated mice by direct injection of UCNs into melanoma tumors or intravenous injection of UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo-targeted PDT agent, this finding may serve as a platform for future noninvasive deep-cancer therapy.
传统的光动力疗法（PDT）受到用于激活它的可见光穿透深度的限制。在这里，我们使用介孔硅包覆的上转换荧光纳米粒子（UCNs）作为纳米换能器，将深穿透近红外光转换为可见波长，并作为光敏剂的载体。我们还利用 UCN 在单一激发波长下的多色发射能力，同时激活两种光敏剂以增强 PDT。与使用单一光敏剂的方法相比，我们通过增强单线态氧的生成和降低细胞活力，显示出双重光敏剂方法具有更高的 PDT 疗效。体内研究还表明，通过将 UCN 直接注射到黑色素瘤肿瘤中或静脉注射与肿瘤靶向剂结合的 UCN 到荷瘤小鼠中，可抑制 PDT 治疗后的肿瘤生长。据我们所知，这是首次将负载光敏剂的 UCN 作为体内靶向 PDT 剂进行展示，这一发现可能为未来的非侵入性深层癌症治疗提供一个平台。
