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首页> 外文期刊>Biomaterials Science >Combinatorial miRNA-34a replenishment and irinotecan delivery via auto-fluorescent polymeric hybrid micelles for synchronous colorectal cancer theranostics
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Combinatorial miRNA-34a replenishment and irinotecan delivery via auto-fluorescent polymeric hybrid micelles for synchronous colorectal cancer theranostics

机译：通过自动荧光聚合物杂交胶束进行组合MiRNA-34A补充和伊替康递送，用于同步结直肠癌Theranostics

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摘要

The synergistic combination of microRNA (miRNA) modulation and chemotherapy has emerged as an effective strategy to combat cancer. Irinotecan (IRI) is a potent antitumor chemotherapeutic in clinical practice and has been used for treating various malignant tumors, including colorectal cancer (CRC). However, IRI is not effective for advanced CRC or metastatic behavior. Herein, novel polymeric hybrid micelles were engineered based on two different amphiphilic copolymers, polyethyleneimine-poly(D,Llactide) (PEI-PLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethyleneglycol) (DSPE-PEG), in which IRI and a tumor suppressive microRNA-34a (miR-34a) gene were efficiently co-loaded (MINPs) to achieve a chemo-miRNA combination therapy against CRC. MINPs were successfully constructed by two-step film dispersion and electrostatic interaction methods. IRI and miR-34a could be efficaciously encapsulated as MINPs and transferred to CRC cells. After encapsulation, MINPs would then upregulate miR-34a expression and regulate miR-34a-related downstream genes, which in turn led to enhanced cell cytotoxicity and apoptosis ratios. MINPs presented an excitationdependent multi-wavelength emission feature due to the intrinstic fluorescence properties of PEI-PLA and could be utilized for in vitro/vivo imaging. According to the in vivo experimental results, MINPs possess the great characteristic of accumulating in situ in a tumor site and lightening it after intravenous administration. Furthermore, MINPs presented extraordinary antitumor efficacy owing to the combined therapy effects of IRI and miR-34a with good biocompability. Overall, our findings validated MINPsmediated miR-34a replenishment and IRI co-delivery to serve as an effective theranostic platform and provided an innovative horizon for combining chemo-gene therapy against CRC.
机译：MicroRNA（miRNA）调节和化学疗法的协同组合已成为对抗癌症的有效策略。 Irinotecan（IRI）是临床实践中有效的抗肿瘤化学治疗方法，已用于治疗各种恶性肿瘤，包括结肠直肠癌（CRC）。然而，IRI对高级CRC或转移性行为无效。在此，基于两种不同的两亲性共聚物，聚乙烯亚胺 - 聚（D，Llactide）（PEI-PLA）和1,2-Distearoyl-Sn-甘油-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇），改造了新型聚合物杂交胶束。 - 磷酸乙醇胺（聚乙二醇） （DSPE-PEG），其中IRI和肿瘤抑制MICRRNA-34A（MIR-34A）基因有效地加载（MINPS），以实现对CRC的化学 - miRNA联合疗法。通过两步膜分散和静电相互作用方法成功构建了Minps。 IRI和MIR-34A可以致力于肿瘤中染色并转移至CRC细胞。在封装后，小酸地将上调miR-34a表达并调节miR-34a相关的下游基因，这反过来导致细胞细胞毒性和凋亡比增强。由于PEI-PLA的内部荧光特性，MINAP提出了激发依赖的多波长发射特征，并且可以用于体外/体内成像。根据体内实验结果，MINAP具有在肿瘤部位累积的巨大特征，并在静脉内给药后闪电。此外，由于IRI和miR-34a具有良好的生物编译，Minps呈现出非凡的抗肿瘤效果。总体而言，我们的调查结果经过验证了MIL-34A补充和IRI共同交付，作为一种有效的治疗平台，并为CRC组合化学基因治疗，提供了一种创新的地平线。

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  • 来源
    《Biomaterials Science》 |2020年第24期|共13页
  • 作者

    Yunhao Li; Fan Jia; Xiongwei Deng; Xuan Wang; Jianqing Lu; Leihou Shao; Xinyue Cui; Zian Pan; Yan Wu;

  • 作者单位

    Department of General Surgery Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

    CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 P. R. China;

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