Department of Chemistry and Biochemistry, University of Mississippi, University, MS 38677, USA.
Department of BioMolecular Sciences, University of Mississippi, University, MS 38677, USA.
Nanoscale. 2024 Mar 14;16(11):5584-5600. doi: 10.1039/d3nr06349f.
Zwitterionic-based systems offer promise as next-generation drug delivery biomaterials capable of enhancing nanoparticle (NP) stimuli-responsiveness, biorecognition, and biocompatibility. Further, imidazole-functionalized amphiphilic zwitterions are able to readily bind to various biological macromolecules, enabling antifouling properties for enhanced drug delivery efficacy and bio-targeting. Herein, we describe structurally tuned zwitterionic imidazole-based ionic liquid (ZIL)-coated PEG-PLGA nanoparticles made with sonicated nanoprecipitation. Upon ZIL surface modification, the hydrodynamic radius increased by nearly 20 nm, and the surface charge significantly shifted closer to neutral. H NMR spectra suggests that the amount of ZIL on the nanoparticle surface is controlled by the structure of the ZIL and that the assembly occurs as a result of non-covalent interactions of ZIL-coated nanoparticle with the polymer surface. These nanoparticle-zwitterionic liquid (ZIL) constructs demonstrate selective affinity towards red blood cells in whole mouse blood and show relatively low human hemolysis at ∼5%. Additionally, we observe higher nanoparticle accumulation of ZIL-NPs compared with unmodified NP controls in human triple-negative breast cancer cells (MDA-MB-231). Furthermore, although the ZIL shows similar protein adsorption by SDS-PAGE, LC-MS/MS protein analysis data demonstrate a difference in the relative abundance and depletion of proteins in mouse and human serum. Hence, we show that ZIL-coated nanoparticles provide a new potential platform to enhance RBC-based drug delivery systems for cancer treatments.
两性离子基系统作为下一代药物输送生物材料具有很大的应用前景，能够提高纳米粒子（NP）的刺激响应性、生物识别性和生物相容性。此外，咪唑功能化的两亲性两性离子能够轻易地与各种生物大分子结合，从而赋予抗污染特性，提高药物输送效率和生物靶向性。在此，我们描述了通过超声纳米沉淀制备的结构可调的两性离子咪唑基离子液体（ZIL）包覆的 PEG-PLGA 纳米粒子。经过 ZIL 表面改性后，水动力学半径增加了近 20nm，表面电荷显著向中性靠近。1H NMR 谱表明，ZIL 在纳米粒子表面的量受 ZIL 结构控制，组装是由于 ZIL 包覆的纳米粒子与聚合物表面的非共价相互作用而发生的。这些纳米粒子-两性离子液体（ZIL）结构在全鼠血中对红细胞表现出选择性亲和力，在约 5%时显示出相对较低的人红细胞溶血率。此外，我们观察到 ZIL-NP 在人三阴性乳腺癌细胞（MDA-MB-231）中的积累量高于未修饰的 NP 对照。此外，尽管 ZIL 通过 SDS-PAGE 显示出相似的蛋白质吸附，但 LC-MS/MS 蛋白质分析数据表明，在小鼠和人血清中，蛋白质的相对丰度和耗竭存在差异。因此，我们表明 ZIL 包覆的纳米粒子为增强基于红细胞的癌症治疗药物输送系统提供了一个新的潜在平台。
