Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Material Technology and Engineering, Ningbo 315201, PR China; The School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, PR China.
Key Laboratory of Magnetic Materials and Devices & Division of Functional Materials and Nanodevices, Ningbo Institute of Material Technology and Engineering, Ningbo 315201, PR China; Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, PR China.
Biomaterials. 2015 Mar;44:82-90. doi: 10.1016/j.biomaterials.2014.12.040. Epub 2015 Jan 12.
Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL) nanocomposites have potential application for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT) of cancers using the light stability and biocompatibility of TiO2 inorganic photosensitizer. However, TiO2 inorganic photosensitizer could only be excited by ultraviolet (UV) light, which was harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted NaGdF4:Yb/Tm@SiO2@TiO2 nanocomposites (FA-Gd-Si-Ti NPs) were constructed and synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic PDT, in which TiO2 component could be excited by NIR light due to the UCL performance of NaGdF4:Yb/Tm component converting NIR to UV light. The results showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T1-weighted MRI contrast agents with high longitudinal relaxivity (r1) of 4.53 mm(-1) s(-1), also in vivo MRI of nude mice showed "bright" signal in MCF-7 tumor. Under the irradiation of 980 nm laser at the power density of 0.6 W/cm(2) for 20 min, the viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice model showed that the inhibition ratio of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with that of nude mice in control group. Based on the deep penetration of NIR light and the good biocompatibility of TiO2 inorganic photosensitizer, the as-prepared FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive PDT of cancers in deep tissues.
无机光敏剂偶联的基于 Gd 的上转换发光（UCL）纳米复合材料具有用于癌症的磁共振成像（MRI）和光动力疗法（PDT）的双重应用潜力，其利用 TiO2 无机光敏剂的稳定性和生物相容性。然而，TiO2 无机光敏剂只能被紫外（UV）光激发，而紫外光在组织中具有危害性且穿透力较弱。在这项工作中，构建并合成了叶酸（FA）靶向的 NaGdF4:Yb/Tm@SiO2@TiO2 纳米复合材料（FA-Gd-Si-Ti NPs），用于体内 MRI 和近红外（NIR）响应的无机 PDT，其中 NaGdF4:Yb/Tm 组件的 UCL 性能可将 NIR 光转换为 UV 光，从而使 TiO2 组件能够被 NIR 光激发。结果表明，所制备的 FA-Gd-Si-Ti NPs 在体外和体内具有良好的生物相容性。此外，MR 研究表明，FA-Gd-Si-Ti NPs 是良好的 T1 加权 MRI 对比剂，纵向弛豫率（r1）高达 4.53 mm-1 s-1，裸鼠体内 MRI 也显示 MCF-7 肿瘤呈“亮”信号。在 980nm 激光照射下，功率密度为 0.6W/cm2，照射 20min 后，与 FA-Gd-Si-Ti NPs 孵育的 HeLa 和 MCF-7 细胞的存活率分别从约 90%降至 35%和 31%。此外，在 MCF-7 荷瘤裸鼠模型的体内 PDT 中，与对照组的裸鼠相比，注射 FA-Gd-Si-Ti NPs 的肿瘤抑制率在 2 周治疗后达到 88.6%。基于 NIR 光的深穿透性和 TiO2 无机光敏剂的良好生物相容性，所制备的 FA-Gd-Si-Ti NPs 可能在深部组织的癌症的 MRI 和 NIR 响应 PDT 中具有潜在应用。
