In vivo synergistic antitumor effect and safety of siRNA and lonidamine dual-loaded hierarchical targeted nanoparticles
In vivo synergistic antitumor effect and safety of siRNA and lonidamine dual-loaded hierarchical targeted nanoparticles
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siRNA与氯尼达明双载分级靶向纳米粒子的体内协同抗肿瘤作用及安全性
DOI：
10.1016/j.ijpharm.2016.04.056
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发表时间：
2016-06-15
影响因子：
5.8
通讯作者：
Jiang, Hu-Lin
中科院分区：
文献类型：
--
作者：
Zhang, Bing-Feng;Xing, Lei;Jiang, Hu-Lin
基于纳米给药系统的发展，化疗药物与小干扰RNA（siRNA）联合给药在肿瘤治疗中显示出了巨大的优势。本研究评价了siRNA与氯尼达明（LND）联合递药系统的协同治疗优势和安全性。通过H22皮下肉瘤模型评价聚合物-共混物纳米载体的体内肿瘤蓄积能力和肿瘤生长抑制效果。此外，比较来自各组的肿瘤切片的苏木精和伊红（H&E）染色和转移酶介导的dUTP缺口末端标记（TUNEL）染色以评估治疗功效。双载纳米载体具有更好的肿瘤蓄积能力，协同作用显著抑制实体瘤生长，甚至显著降低LND的肝毒性，具有良好的体内生物相容性，而LND单载则表现出严重的肝毒性。我们认为，具有高效性和生物相容性的双层载药递药系统将为肿瘤的联合治疗提供一种有希望的途径。(c)2016爱思唯尔B. V.保留所有权利。
Based on development of nano-delivery system, co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) has exerted a promising advantage in cancer therapy. In this work, the superiority of synergistic therapy and safety of the hierarchical targeted co-delivery system loaded with siRNA and lonidamine (LND) were evaluated. The in vivo tumor accumulation ability and cancer growth inhibition effect of the polymer-blend nanocarriers were evaluated by a H22 subcutaneous sarcoma model. Moreover, hematoxylin and eosin (H&E) staining and transferase-mediated dUTP nick endlabeling (TUNEL) staining of tumor sections from each group were compared to assess the therapeutic efficacy. The dual-loaded nanocarriers had better tumor accumulation ability, remarkably inhibited growth of solid tumor in a synergistic manner, even significantly decreased hepatotoxicity of LND, and had good in vivo biocompatibility whereas LND alone showed serious hepatotoxicity. We believed that the dual-loaded hierarchical targeted delivery system with high effectiveness and biocompatibility would provide a promising approach for cancer combination therapy. (c) 2016 Elsevier B.V. All rights reserved.