Hyaluronic acid-chitosan nanoparticles for co-delivery of M1R-34a and doxorubicin in therapy against triple negative breast cancer
Hyaluronic acid-chitosan nanoparticles for co-delivery of M1R-34a and doxorubicin in therapy against triple negative breast cancer
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DOI：
10.1016/j.biomaterials.2014.02.006
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发表时间：
2014-05-01
期刊：
影响因子：
14
通讯作者：
Zeng, Yi
中科院分区：
文献类型：
--
作者：
Deng, Xiongwei;Cao, Minjun;Zeng, Yi
转移复发、癌细胞耐药和化疗药物的不良反应是三阴性乳腺癌有效化疗的主要障碍。为了解决这些问题，miR-34 a，一种有效的内源性肿瘤抑制分子在乳腺癌中，与阿霉素（DOX）共封装到透明质酸（HA）-壳聚糖（CS）纳米颗粒（NPs）中，并同时递送到乳腺癌细胞中以改善药物的治疗效果。通过离子凝胶法在水中成功地制备了DOX-miR-34 a共负载的HA-CS NP。体内外实验表明，miR-34 a和DOX可以有效地包裹在HA-CS纳米粒中，并递送到肿瘤细胞或肿瘤组织中，通过抑制非泵抵抗和抗凋亡原癌基因BcI-2的表达，增强DOX的抗肿瘤作用。此外，miR-34 a的细胞内恢复通过靶向Notch-I信号传导抑制乳腺癌细胞迁移。所获得的数据表明，DOX和miR-34 a的共递送可以实现对肿瘤抑制的协同效应，并且基于纳米系统的肿瘤抑制性miRNA和化疗剂的共递送可能是用于增强抗肿瘤治疗的有希望的组合治疗策略。(C)2014爱思唯尔有限公司版权所有。
Metastatic relapse, development of drug resistance in cancer cells and adverse side effects of chemotherapeutic agents are the major obstacles for effective chemotherapy against triple-negative breast cancer. To address these problems, miR-34a, a potent endogenous tumor suppressive molecule in breast cancer, was co-encapsulated with doxorubicin (DOX) into hyaluronic acid (HA)-chitosan (CS) nanoparticles (NPs) and simultaneously delivered into breast cancer cells for improved therapeutic effects of drug. DOX-miR-34a co-loaded HA-CS NPs were successfully prepared through ionotropic gelation method in water. In vitro and in vivo experiments showed that miR-34a and DOX can be efficiently encapsulated into HA-CS NPs and delivered into tumor cells or tumor tissues and enhance anti-tumor effects of DOX by suppressing the expression of non-pump resistance and anti-apoptosis proto-oncogene BcI-2. In addition, intracellular restoration of miR-34a inhibited breast cancer cell migration via targeting Notch-I signaling. The obtained data suggest that co-delivery of DOX and miR-34a could achieve synergistic effects on tumor suppression and nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy. (C) 2014 Elsevier Ltd. All rights reserved.