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首页> 外文期刊>RSC Advances >A pH sensitive co-delivery system of siRNA and doxorubicin for pulmonary administration to B16F10 metastatic lung cancer
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A pH sensitive co-delivery system of siRNA and doxorubicin for pulmonary administration to B16F10 metastatic lung cancer

机译：SiRNA和多柔比星的pH敏感共递送系统，用于B16F10转移性肺癌

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摘要

Pulmonary co-delivery to the lungs offers a potential therapy for pulmonary diseases. In this study, doxorubicin was conjugated to polyethyleneimine by hydrazone bonds to form a pH sensitive conjugate (PEI-HZ-DOX). A co-delivery carrier was constructed by complexing Bcl2 siRNA with PEI-HZ-DOX. The complex particles could be used by pulmonary administration for metastatic lung cancer treatment. DOX release from the PEI-HZ-DOX conjugate was in a pH-dependent pattern and accelerated by decreasing pH. The cell uptake of DOX and siRNA from PEI-HZ-DOX/siRNA and efficient intracellular release of DOX from PEI-HZ-DOX in B16F10 cells were further confirmed. Cell apoptosis and antitumor effects of the combined therapy were evaluated in vitro, the results showed that co-delivery of DOX and siRNA had better antitumor efficacy than mono-delivery of DOX or siRNA. Furthermore, the biodistribution results showed that pulmonary administration could improve the deposition amounts of DOX and siRNA in the lungs and prolong the retention time compared with systemic administration, which demonstrated that the present delivery system is suitable for pulmonary co-delivery. Overall, pH sensitive PEI-HZ-DOX/siRNA complex nanoparticles exhibit great potential for clinical combination therapy of lung cancer by pulmonary administration in local delivery strategies.
机译：肺部递送给肺部为肺部疾病提供潜在的疗法。在该研究中，通过腙键将多柔比星与聚乙烯亚胺缀合，形成pH敏感缀合物（PEI-HZ-DOX）。共递送载体通过用PEI-HZ-DOX络合BCL2 siRNA来构建。复合颗粒可以通过肺部给药进行转移性肺癌治疗方法。从PEI-HZ-DOX缀合物中的DOX释放是pH依赖性图案，并通过降低pH加速。进一步证实了来自PEI-HZ-DOX / siRNA / siRNA的DOX和siRNA的细胞吸收，从B16F10细胞中的PEI-HZ-DOx提供了高效的细胞内释放。在体外评估细胞凋亡和组合治疗的抗肿瘤效应，结果表明，DOX和siRNA的共递送比DOX或siRNA的单递送更好的抗肿瘤效力。此外，生物分布结果表明，肺部给药可以改善肺中DOX和siRNA的沉积量并延长与全身给药相比的保留时间，这证明了本递送系统适用于肺部共递送。总体而言，pH敏感的PEI-Hz-DOX / siRNA复合纳米颗粒在局部交付策略中表现出肺癌肺癌临床联合治疗的巨大潜力。

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  • 来源
    《RSC Advances》 |2015年第125期|共6页
  • 作者

    Xu Caina; Tian Huayu; Sun Hai; Jiao Zixue; Zhang Ying; Chen Xuesi;

  • 作者单位

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

    Chinese Acad Sci Changchun Inst Appl Chem Key Lab Polymer Ecomat Changchun 130022 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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