Aptamer-Dendrimer Functionalized Magnetic Nano-Octahedrons: Theranostic Drug/Gene Delivery Platform for Near-Infrared/Magnetic Resonance Imaging-Guided Magnetochemotherapy
Aptamer-Dendrimer Functionalized Magnetic Nano-Octahedrons: Theranostic Drug/Gene Delivery Platform for Near-Infrared/Magnetic Resonance Imaging-Guided Magnetochemotherapy
复制标题
适体-树枝状聚合物功能化磁性纳米八面体：用于近红外/磁共振成像引导磁化疗的治疗诊断药物/基因递送平台。
DOI：
10.1021/acsnano.1c06667
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发表时间：
2021-09-29
期刊：
影响因子：
17.1
通讯作者：
Liu, Yiyao
中科院分区：
文献类型：
--
作者：
Chen, Zhongyuan;Peng, Yueting;Liu, Yiyao
在纳米系统中结合磁热疗和化学疗法被认为是一种有前途的癌症治疗方法。然而，磁性纳米粒子在生理环境中的非特异性积累和快速清除限制了其进一步的生物医学应用。在此，我们报告了一种高选择性的治疗诊断纳米复合物，ZIPP-Apt：DOX/siHSPs，由超顺磁性锌掺杂的氧化铁纳米八面体核心，阳离子PAMAM树状聚合物和功能性表面修饰如PEG，AS 1411适配体和荧光标签（FITC或Cy5.5），以及疏水性抗癌药物阿霉素（DOX）和HSP 70/HSP 90 siRNA的负载构建。我们的研究结果表明，由于AS 1411-核仁素的亲和力，ZIPP-Apt：DOX/siHSPs的细胞摄取和肿瘤特异性积累显著增加，并进一步证实了HSP 70和HSP 90的同时耗竭在体外和体内均敏化磁热疗和化疗诱导的细胞死亡。总而言之，我们的研究为适体靶向，NIR/MR双模态成像引导和HSP 70/HSP 90沉默敏化的磁化学疗法提供了一个治疗诊断纳米平台，这有可能推动多功能磁性纳米系统向临床应用发展。
The combination of magnetic hyperthermia and chemotherapy within a nanosystem is thought to be a promising approach for cancer therapies. However, the nonspecific accumulation and fast clearance of magnetic nanoparticles in the physiological environment limited their further biomedical applications. Herein, we report a highly selective theranostic nanocomplex, ZIPP-Apt:DOX/siHSPs, built with superparamagnetic zinc-doped iron oxide nano-octahedral core, cationic PAMAM dendrimer, and functional surface modifications such as PEG, AS1411 aptamer, and fluorescent tags (FITC or Cy5.5), together with the loading of hydrophobic anticancer drug doxorubicin (DOX) and HSP70/HSP90 siRNAs. Our results demonstrate that the cellular uptake and the tumor-specific accumulation of ZIPP-Apt:DOX/siHSPs were significantly increased due to the AS1411-nucleolin affinity and further confirmed that the simultaneous depletion of HSP70 and HSP90 sensitized magnetic hyperthermia and chemotherapy-induced cell death both in vitro and in vivo. Altogether, our study provides a theranostic nanoplatform for aptamer-targeted, NIR/MR dual-modality imaging guided, and HSP70/HSP90 silencing sensitized magnetochemotherapy, which has the potential to advance versatile magnetic nanosystems toward clinical applications.