Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Small. 2018 Dec;14(49):e1802904. doi: 10.1002/smll.201802904. Epub 2018 Oct 25.
Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine. However, a critical challenge remains in the rational fabrication of monodisperse multicomponent nanoparticles with enhanced multifunctional characteristics for efficient cancer theranostics. Here, a rational and facile synthesis of monodisperse Gd O /Bi S hybrid nanodots (Gd/Bi-NDs) is demonstrated as a multifunctional nanotheranostic agent using a albumin nanoreactor for computed tomography (CT)/photoacoustics (PA)/magnetic resonance (MR) imaging and simultaneous photothermal tumor ablation. Two nanoprecipitation reactions in one albumin nanoreactor are simultaneously conducted to generate ultrasmall Gd/Bi-NDs with both orthorhombic Bi S and cubic Gd O nanostructures. Their hybrid nanostructure generates distinctly enhanced longitudinal relaxivity in the spatially confined albumin nanocage as compared to monocomponent Gd O nanodots. Moreover, such hybrid nanodots possess multiple desirable characteristics including superior photobleaching resistance, efficient cellular uptake, preferable tumor accumulation, good in vivo clearance, and negligible acute toxicity, thereby leading to complementary PA/CT/MR imaging with spatial and anatomic characteristics, as well as effective photothermal tumor ablation without regrowth. These results represent a promising approach to fabricate monodisperse multicomponent nanotheranostic agents for efficient cancer theranostics.
多功能纳米诊疗剂在精准纳米医学领域具有重要意义。然而，合理制备具有增强多功能特性的单分散多组分纳米粒子仍然是一个关键挑战，这对于高效的癌症诊疗至关重要。在此，我们展示了一种使用白蛋白纳米反应器合理且简便的方法来合成单分散 GdO/BiS 杂化纳米点（Gd/Bi-NDs），作为一种多功能纳米诊疗剂，用于计算机断层扫描（CT）/光声（PA）/磁共振（MR）成像以及同时进行光热肿瘤消融。在一个白蛋白纳米反应器中同时进行两个纳米沉淀反应，生成具有正交相 BiS 和立方相 GdO 纳米结构的超小 Gd/Bi-NDs。与单一组分 GdO 纳米点相比，它们的杂化纳米结构在空间受限的白蛋白纳米笼中产生明显增强的纵向弛豫率。此外，这些杂化纳米点具有多个理想的特性，包括优异的光漂白抗性、高效的细胞摄取、较好的肿瘤积累、良好的体内清除率和可忽略的急性毒性，从而实现具有空间和解剖特征的互补 PA/CT/MR 成像以及有效的光热肿瘤消融而无复发。这些结果代表了一种制备高效癌症诊疗用单分散多组分纳米诊疗剂的有前途的方法。
