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Poly(2-oxazoline)-magnetite NanoFerrogels: Magnetic field responsive theranostic platform for cancer drug delivery and imaging
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2021-09-13 , DOI: 10.1016/j.nano.2021.102459
Youngee Seo 1 , Lida Ghazanfari 1 , Alyssa Master 1 , Hemant M Vishwasrao 2 , Xiaomeng Wan 1 , Marina Sokolsky-Papkov 1 , Alexander V Kabanov 3
Affiliation  

Combining diagnosis and treatment approaches in one entity is the goal of theranostics for cancer therapy. Magnetic nanoparticles have been extensively used as contrast agents for nuclear magnetic resonance imaging as well as drug carriers and remote actuation agents. Poly(2-oxazoline)-based polymeric micelles, which have been shown to efficiently solubilize hydrophobic drugs and drug combinations, have high loading capacity (above 40% w/w) for paclitaxel. In this study, we report the development of novel theranostic system, NanoFerrogels, which is designed to capitalize on the magnetic nanoparticle properties as imaging agents and the poly(2-oxazoline)-based micelles as drug loading compartment. We developed six formulations with magnetic nanoparticle content of 0.3%-12% (w/w), with the z-average sizes of 85-130 nm and ξ-potential of 2.7-28.3 mV. The release profiles of paclitaxel from NanoFerrogels were notably dependent on the degree of dopamine grafting on poly(2-oxazoline)-based micelles. Paclitaxel loaded NanoFerrogels showed efficacy against three breast cancer lines which was comparable to free paclitaxel. They also showed improved tumor and lymph node accumulation and signal reduction in vivo (2.7% in tumor; 8.5% in lymph node) compared to clinically approved imaging agent ferumoxytol (FERAHEME®) 24 h after administration. NanoFerrogels responded to super-low frequency alternating current magnetic field (50 kA m−1, 50 Hz) which accelerated drug release from paclitaxel-loaded NanoFerrogels or caused death of cells loaded with NanoFerrogels. These proof-of-concept experiments demonstrate that NanoFerrogels have potential as remotely actuated theranostic platform for cancer diagnosis and treatment.



中文翻译:


聚(2-恶唑啉)-磁铁矿 NanoFerrogels:用于癌症药物输送和成像的磁场响应治疗诊断平台



将诊断和治疗方法结合在一个实体中是癌症治疗治疗诊断学的目标。磁性纳米粒子已广泛用作核磁共振成像的造影剂以及药物载体和远程驱动剂。基于聚(2-恶唑啉)的聚合物胶束已被证明可以有效溶解疏水性药物和药物组合,对紫杉醇具有高负载能力(超过 40% w/w)。在这项研究中,我们报告了新型治疗诊断系统 NanoFerrogels 的开发,该系统旨在利用磁性纳米颗粒的特性作为显像剂,并利用聚(2-恶唑啉)基胶束作为药物装载室。我们开发了六种配方,磁性纳米颗粒含量为 0.3%-12% (w/w),z 平均尺寸为 85-130 nm, ζ 电位为 2.7-28.3 mV。 NanoFerrogels 中紫杉醇的释放曲线明显取决于聚 (2-恶唑啉) 胶束上多巴胺的接枝程度。负载紫杉醇的 NanoFerrogels 对三种乳腺癌细胞系显示出与游离紫杉醇相当的功效。与临床批准的显像剂 ferumoxytol (FERAHEME®) 相比,给药 24 小时后,它们还显示出体内肿瘤和淋巴结积聚的改善以及信号减少(肿瘤中 2.7%;淋巴结中 8.5%)。 NanoFerrogels对超低频交流磁场(50 kA m -1 ,50 Hz)有反应,加速了载有紫杉醇的NanoFerrogels的药物释放或导致载有NanoFerrogels的细胞死亡。这些概念验证实验表明,NanoFerrogels 有潜力作为癌症诊断和治疗的远程驱动治疗诊断平台。

更新日期:2021-10-14
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