Clickable and imageable multiblock polymer micelles with magnetically guided and PEG-switched targeting and release property for precise tumor theranosis
Clickable and imageable multiblock polymer micelles with magnetically guided and PEG-switched targeting and release property for precise tumor theranosis
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可点击和可成像的多嵌段聚合物胶束，具有磁引导和 PEG 切换的靶向和释放特性，可实现精确的肿瘤治疗
DOI：
10.1016/j.biomaterials.2017.08.005
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发表时间：
2017-11-01
期刊：
影响因子：
14
通讯作者：
Fu, Qiang
中科院分区：
文献类型：
--
作者：
Wei, Jing;Shuai, Xiaoyu;Fu, Qiang
使用纳米技术的治疗和诊断的靶向递送具有极大的希望，可以最大限度地减少常规化疗的副作用，并实现疾病的特异性和实时检测。为了实现这一目标，我们报告了一个可点击和成像的多嵌段聚氨酯（MPU）组装的纳米车辆。聚合物的软链段基于可分离的聚（乙二醇）（PEG）和可降解的聚（ε-己内酯）（PCL），硬链段由带有还原响应性二硫键和点击活性炔基部分的赖氨酸和胱氨酸衍生物构成，允许通过点击化学进行靶向配体的后缀合。研究发现，带有pH敏感的苯甲酸-亚胺键（BPEG）的PEG冠的切割可以充当开关，其能够在细胞外酸性条件下激活点击的靶向配体，随后触发肿瘤细胞内的核心降解和有效载荷释放。与聚集在胶束核心内的超顺磁性氧化铁纳米颗粒（SPION）组合，MPU在体外表现出优异的磁共振成像（MRI）对比效果和T-2弛豫，以及磁引导的MR成像和多模式靶向治疗剂精确地靶向肿瘤，从而显著抑制癌症，副作用最小。这项工作为智能治疗诊断系统的进一步开发提供了一个安全和通用的平台，用于潜在的磁靶向和成像引导的个性化医疗。(C)2017爱思唯尔有限公司版权所有
Targeted delivery of therapeutics and diagnostics using nanotechnology holds great promise to minimize the side effects of conventional chemotherapy and enable specific and real-time detection of diseases. To realize this goal, we report a clickable and imageable nanovehicle assembled from multiblock polyurethanes (MPUs). The soft segments of the polymers are based on detachable poly(ethylene glycol) (PEG) and degradable poly(epsilon-caprolactone) (PCL), and the hard segments are constructed from lysine and cystine-derivatives bearing reduction-responsive disulfide linkages and click-active alkynyl moieties, allowing for post-conjugation of targeting ligands via a click chemistry. It was found that the cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage (BPEG) could act as an on-off switch, which is capable of activating the clicked targeting ligands under extracellular acidic condition, followed by triggering the core degradation and payload release within tumor cells. In combination with super paramagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T-2 relaxation in vitro, as well as magnetically guided MR imaging and multimodal targeting of therapeutics to tumor precisely, leading to significant inhibition of cancer with minimal side effect. This work provides a safe and versatile platform for the further development of smart theranostic systems for potential magnetically-targeted and imaging-guided personalized medicine. (C) 2017 Elsevier Ltd. All rights reserved.