State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Chemistry, Chemical Engineering and Biotechnology , Donghua University , Shanghai 201620 , P. R. China.
Department of Radiology, Shanghai Public Health Clinical Center , Fudan University , Shanghai 201508 , P. R. China.
ACS Appl Mater Interfaces. 2019 May 1;11(17):15212-15221. doi: 10.1021/acsami.8b21679. Epub 2019 Apr 22.
Design of dual mode or multimode contrast agents or nanoplatforms with antifouling properties is crucial for improved cancer diagnosis since the antifouling materials are able to escape the clearance of the reticuloendothelial system with improved pharmacokinetics. Herein, we present the creation of zwitterionic gadolinium(III) (Gd(III))-complexed dendrimer-entrapped gold nanoparticles (Au DEN) for enhanced dual mode computed tomography (CT)/magnetic resonance (MR) imaging of lung cancer metastasis. In the present work, poly(amidoamine) (PAMAM) dendrimers of generation 5 were partially decorated with carboxybetanie acrylamide (CBAA), 2-methacryloyloxyethyl phosphorylcholine (MPC), and 1,3-propane sultone (1,3-PS), respectively at different degrees, then used to entrap Au NPs within their interiors, and finally acetylated to cover their remaining amine termini. Through protein resistance, macrophage cellular uptake, and pharmacokinetics assays, we show that zwitterionic Au DEN modified with 1,3-PS exhibit the best antifouling property with the longest half-decay time (37.07 h) when compared to the CBAA- and MPC-modified Au DEN. Furthermore, with the optimized zwitterion type, we then prepared zwitterionic Gd(III)-loaded Au DEN modified with arginine-glycine-aspartic acid peptide for targeted dual mode CT/MR imaging of a lung cancer metastasis model. We disclose that the designed multifunctional Au DEN having an Au core size of 2.7 nm and a surface potential of 7.6 ± 0.9 mV display a good X-ray attenuation property, relatively high r relaxivity (13.17 mM s), acceptable cytocompatibility, and targeting specificity to αβ integrin-expressing cancer cells and enable effective dual mode CT/MR imaging of a lung cancer metastasis model in vivo. The developed multifunctional zwitterion-functionalized Au DEN may be potentially adopted as an effective nanoprobe for enhanced dual-modal CT/MR imaging of other cancer types.
设计具有抗污染性能的双模或多模对比剂或纳米平台对于提高癌症诊断水平至关重要，因为抗污染材料能够改善药代动力学，从而逃避网状内皮系统的清除。在此，我们提出了一种两性离子型钆（III）（Gd（III））-配合的树枝状大分子包埋金纳米粒子（Au DEN）的设计，用于增强肺癌转移的双模式计算机断层扫描（CT）/磁共振（MR）成像。在本工作中，聚（酰胺-胺）（PAMAM）树枝状大分子的第 5 代分别用羧基甜菜碱丙烯酰胺（CBAA）、2-甲基丙烯酰氧乙基磷酸胆碱（MPC）和 1,3-丙烷磺内酯（1,3-PS）进行部分修饰，然后分别用于在其内部包埋 Au NPs，最后乙酰化以覆盖其剩余的胺端。通过蛋白质抗性、巨噬细胞摄取和药代动力学实验，我们表明，与 CBAA 和 MPC 修饰的 Au DEN 相比，用 1,3-PS 修饰的两性离子型 Au DEN 具有最佳的抗污染性能，半衰期最长（37.07 h）。此外，在优化了两性离子类型后，我们然后制备了用精氨酸-甘氨酸-天冬氨酸肽修饰的载有两性离子 Gd（III）的 Au DEN，用于肺癌转移模型的靶向双模式 CT/MR 成像。我们揭示，设计的具有 2.7nm Au 核尺寸和 7.6±0.9mV 表面电势的多功能 Au DEN 具有良好的 X 射线衰减性能、相对较高的 r1 relaxivity（13.17 mM s）、可接受的细胞相容性和对表达αβ整合素的癌细胞的靶向特异性，并能够有效地进行肺癌转移模型的双模式 CT/MR 成像。开发的多功能两性离子功能化 Au DEN 可作为增强其他癌症类型的双模态 CT/MR 成像的有效纳米探针。
