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, People's Republic of China.
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201620, People's Republic of China.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1803-1812. doi: 10.1021/acsabm.0c01525. Epub 2021 Jan 18.
Development of multifunctional nanoprobes with an excellent imaging performance for precision tumor imaging still remains a great challenge. Here, we report the creation of multifunctional core-shell tecto dendrimers (CSTDs) incorporated with gold nanoparticles (Au NPs) as a platform for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, β-cyclodextrin (CD)-modified generation 5 poly(amidoamine) (PAMAM) dendrimers were synthesized and entrapped with Au NPs as the core. Then, adamantine (Ad)-modified generation 3 PAMAM dendrimers acted as a shell to form Au NP-entrapped CSTDs (for short, Au CSTDs) through supramolecular host-guest recognition between CD and Ad. The formed Au CSTDs were sequentially modified with Arg-Gly-Asp (RGD) peptide through a spacer of polyethylene glycol (PEG), Gd chelator, and 1,3-propane sultone, followed by chelating Gd (III) ions. The synthesized multifunctional Au CSTDs with a mean size of 11.61 nm possess good colloidal stability, high X-ray attenuation property and high relaxivity (9.414 mM s), good antifouling property, and desired cytocompatibility. Due to the RGD-mediated targeting specificity to αβ integrin-overexpressing cancer cells, the multifunctional Au CSTDs enable targeted CT/MR dual mode imaging of a breast cancer model and can be cleared out of body through metabolization pathway with good biosafety profile. The developed multifunctional CSTDs may be applied as an effective CT/MR dual mode imaging probe for accurate diagnosis of various αβ integrin-overexpressing cancer types.
多功能纳米探针具有优异的成像性能，可用于精准肿瘤成像，但仍极具挑战性。在此，我们报告了多功能核壳树状大分子（CSTDs）的构建，其将金纳米颗粒（Au NPs）作为平台，用于肿瘤的双模式计算机断层扫描（CT）/磁共振（MR）成像。在这项工作中，合成了β-环糊精（CD）修饰的第五代聚酰胺胺（PAMAM）树状大分子作为核，并将其包裹在金纳米颗粒中。然后，金刚烷（Ad）修饰的第三代 PAMAM 树状大分子作为壳，通过 CD 和 Ad 之间的超分子主客体识别，形成了金纳米颗粒包裹的 CSTDs（简称 Au CSTDs）。形成的 Au CSTDs 依次通过聚乙二醇（PEG）间隔臂、钆螯合剂和 1,3-丙烷磺内酯进行 RGD 肽修饰，随后螯合 Gd（III）离子。合成的多功能 Au CSTDs 的平均粒径为 11.61nm，具有良好的胶体稳定性、高 X 射线衰减性能和高 r1 值（9.414mM s）、良好的抗污染性和理想的细胞相容性。由于 RGD 介导的对αβ整合素过表达癌细胞的靶向特异性，多功能 Au CSTDs 能够实现乳腺癌模型的靶向 CT/MR 双模式成像，并且可以通过代谢途径从体内清除，具有良好的生物安全性。所开发的多功能 CSTDs 可用作一种有效的 CT/MR 双模式成像探针，用于各种αβ整合素过表达癌症类型的精准诊断。
