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首页> 外文期刊>Advanced Functional Materials >Multifunctional DNA Polycatenane Nanocarriers for Synergistic Targeted Therapy of Multidrug-Resistant Human Leukemia
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Multifunctional DNA Polycatenane Nanocarriers for Synergistic Targeted Therapy of Multidrug-Resistant Human Leukemia

机译：多功能DNA聚catenane纳米载体的多药耐药人类白血病的协同靶向治疗。

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摘要

Chemotherapy, as one of the principal modalities for cancer therapy, is limited by its inefficient delivery, serious side effects as well as multidrug resistance (MDR). Herein, multifunctional aptamer-tethered deoxyribonucleic acids (DNA) polycatenanes (AptDPCs) is reported to combat MDR human leukemia. By rational design, the DNA polycatenanes (DPCs) are first constructed by a one-step self-assembly approach, during which DPCs are incorporated with fluorophores for bioimaging, abundant doxorubicin (DOX) intercalation sites for drug delivery, and antisense oligonucleotides (AS ODNs) for inhibiting the expression of P-glycoprotein (P-gp) and further reversing MDR. In addition, to endow the DPCs with specific recognition toward the target cancer cells and high purity, aptamers are tethered to the DPCs via the magnetic separation method based on the toehold-mediated strand displacement (TMSD) reaction, which not only improves the purity and reproducibility of the AptDPCs, but also realizes the recycle of magnetic carriers. The results confirm that the AptDPCs can deliver drugs and AS ODNs into the target cancer cells and synergistically inhibit the MDR tumor growth without apparent systematic toxicity. The proposed AptDPC-based drug delivery system can effectively reduce side effects and reverse MDR, which provides a promising platform for codelivery of therapeutic genes and chemodrugs in targeted cancer therapy.
机译：化学疗法作为癌症治疗的主要方式之一，受其效率低下，严重的副作用以及多药耐药性（MDR）的限制。在此，据报道，多功能适体束缚的脱氧核糖核酸（DNA）聚catenanes（AptDPC）可以对抗人类多药耐药的人类白血病。通过合理的设计，首先通过一步自组装方法构建DNA聚catenanes（DPC），在此过程中，将DPC与用于生物成像的荧光团，用于药物输送的大量阿霉素（DOX）嵌入位点以及反义寡核苷酸（AS ODN）结合在一起。 ），以抑制P-糖蛋白（P-gp）的表达并进一步逆转MDR。另外，为了赋予DPC对靶癌细胞特异性的识别和高纯度，适体通过基于脚趾介导的链置换（TMSD）反应的磁分离方法与DPC拴在一起，不仅提高了纯度和AptDPC的可重复性，但也实现了磁性载体的回收。结果证实，AptDPC可以将药物和AS ODN传递到靶癌细胞中，并协同抑制MDR肿瘤的生长，而没有明显的系统毒性。所提出的基于AptDPC的药物递送系统可以有效减少副作用并逆转MDR，这为靶向基因治疗中的治疗基因和化学药物的代码递送提供了一个有希望的平台。

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