State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry and Chemical Engineering, Donghua University, Shanghai 201620, China.
College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Biomacromolecules. 2023 Feb 13;24(2):967-976. doi: 10.1021/acs.biomac.2c01403. Epub 2023 Jan 6.
The development of nanoprobes that have amplified enhanced permeability and retention (EPR) effect is crucial for their precise cancer diagnosis performance. Here, we present the development of functional dendrimer-based nanogels (DNGs) with the generation three primary amine-terminated poly(amidoamine) (PAMAM) dendrimers (G3·NH) cross-linked by ,'-bis(acryloyl) cystamine (BAC). The DNGs were prepared through a Michael addition reaction between G3·NH dendrimers and BAC an inverse microemulsion method and entrapped with gold nanoparticles (Au NPs) to form Au-DNGs. The Au-DNGs were sequentially modified with diethylenetriamine penta-acetic acid (DTPA)-gadolinium (Gd) complex, poly(ethylene glycol) (PEG)-linked arginine-glycine-aspartic (RGD) peptide, and 1,3-propanesultone (1,3-PS). The formed multifunctional RGD-Gd@Au-DNGs-PS (R-G@ADP) possessing an average diameter of 122 nm are colloidally stable and display a high X-ray attenuation coefficient, excellent relaxivity (9.13 mM s), desired protein resistance rendered by the zwitterionic modification, and cytocompatibility. With the targeting specificity mediated by RGD and the much better tumor penetration capability than the counterpart material of single dendrimer-entrapped Au NPs, the developed multifunctional R-G@ADP enable targeted and enhanced computed tomography (CT)/magnetic resonance (MR) dual-modal imaging of a pancreatic tumor model . The current work demonstrates a unique design of targeted and zwitterionic DNGs with prolonged blood circulation time as an emerging nanoprobe for specific tumor CT/MR imaging through amplified passive EPR effect.
开发具有增强增强型通透性和保留（EPR）效应的纳米探针对于其精确的癌症诊断性能至关重要。在这里，我们提出了一种功能化树枝状聚合物纳米凝胶（DNG）的开发，该纳米凝胶由第三代伯胺封端的聚酰胺胺（PAMAM）树枝状大分子（G3·NH）通过双（丙烯酰基）胱胺（BAC）交联而成。DNG 通过 G3·NH 树枝状大分子与 BAC 的迈克尔加成反应在反微乳液中制备而成，并包埋金纳米颗粒（Au NPs）以形成 Au-DNG。Au-DNG 依次用二乙三胺五乙酸（DTPA）-钆（Gd）配合物、聚乙二醇（PEG）连接的精氨酸-甘氨酸-天冬氨酸（RGD）肽和 1,3-丙磺内酯（1,3-PS）进行修饰。形成的多功能 RGD-Gd@Au-DNG-PS（R-G@ADP）具有 122nm 的平均直径，胶体稳定，显示出高 X 射线衰减系数、优异的弛豫率（9.13mM s）、由两性离子修饰赋予的良好的蛋白质抗性和细胞相容性。通过 RGD 介导的靶向特异性和比单树枝状大分子包埋的 Au NPs 更好的肿瘤穿透能力，开发的多功能 R-G@ADP 能够对胰腺肿瘤模型进行靶向和增强的计算机断层扫描（CT）/磁共振（MR）双模式成像。目前的工作展示了一种独特的设计，即靶向和两性离子 DNG 具有延长的血液循环时间，作为一种通过放大被动 EPR 效应用于特定肿瘤 CT/MR 成像的新兴纳米探针。
