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(ε-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 superparamagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T₂ 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.

中文翻译：

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具有磁性导向和PEG切换靶向和释放特性的可点击和可成像的多嵌段聚合物胶束，可用于精确的肿瘤治疗

使用纳米技术有针对性地提供治疗和诊断方法，有望最大程度地减少传统化学疗法的副作用，并能够进行特异性和实时的疾病检测。为了实现这一目标，我们报告了一种由多嵌段聚氨酯（MPU）组装而成的可点击且可成像的纳米车辆。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），硬链段由赖氨酸和胱氨酸衍生物构成，具有还原反应性二硫键和点击活性炔基部分，可通过单击化学。发现带有pH敏感的苯甲亚胺键（BPEG）的PEG电晕的裂解可以作为开-关开关，它能够在细胞外酸性条件下激活点击的靶向配体，然后触发核心降解和有效载荷在肿瘤细胞内释放。与胶束核心中聚集的超顺磁性氧化铁纳米粒子（SPION）结合使用时，MPU在体外具有出色的磁共振成像（MRI）对比效果和T ₂弛豫，以及磁引导MR成像和治疗剂精确靶向肿瘤的多模式靶向，可显着抑制癌症，且副作用极小。这项工作为进一步开发用于潜在磁靶向和影像引导的个性化药物的智能治疗系统提供了一个安全且通用的平台。