Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Nanoscale. 2014 Aug 7;6(15):9198-205. doi: 10.1039/c4nr02495h.
Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.
上转换纳米粒子（UCNPs）近年来在癌症成像和治疗领域引起了广泛关注。在此，我们首次报道了使用经过精心设计的表面化学的 UCNPs 进行癌症的光动力治疗（PDT）和基因治疗的联合治疗。在我们的系统中，通过层层策略合成带正电荷的 NaGdF4:Yb,Er UCNPs，并带有多层聚合物涂层，然后同时负载光敏剂 Chlorin e6（Ce6）和针对 Plk1 癌基因的小干扰 RNA（siRNA）。一方面，在 980nm 的近红外（NIR）光激发下，与可见光相比，其组织穿透能力大大提高，可通过 UCNPs 向光敏剂 Ce6 的共振能量转移产生细胞毒性单线态氧，而剩余的上转换发光则用于成像。另一方面，UCNPs 递送的 siRNA 诱导的 Plk1 沉默可诱导显著的癌细胞凋亡。由于这种光动力和基因治疗的联合作用，实现了显著增强的癌细胞杀伤效果。我们的工作因此强调了 UCNPs 用于癌症成像引导联合治疗的前景。
