CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal carcinoma therapy in vivo
CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal carcinoma therapy in vivo
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CD-PLLD 共递送多西紫杉醇和 MMP-9 siRNA 质粒用于鼻咽癌体内治疗
DOI：
10.3892/mmr.2017.6715
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发表时间：
2017-08-01
影响因子：
3.4
通讯作者：
Xie, Minqiang
中科院分区：
文献类型：
--
作者：
Liu, Tao;Wu, Xidong;Xie, Minqiang
药物与靶基因的联合递送已成为癌症治疗的主要策略。在前期研究的基础上，我们合成了一种由β -环糊精（CD）和聚l -赖氨酸树突状体（PLLD）组成的星形共聚物，通过CD-PLLD/DOC/MMP-9复合物，将多西紫杉醇（DOC）和基质金属蛋白酶9 （MMP-9）小干扰RNA在体内共递送至植入人鼻咽癌（NPC）肿瘤细胞的小鼠体内。与常用的两亲共聚物胶束不同，所获得的CD衍生物可以直接用于核酸和疏水DOC的联合递送，而无需复杂的胶束化过程。体内实验表明，CD-PLLD/DOC/MMP-9抑制了HNE-1肿瘤的生长，降低了增殖细胞核抗原的表达水平，表明了一种潜在的鼻咽癌治疗策略。此外，研究了DOC和MMP-9的分布；CD-PLLD/DOC/MMP-9复合物在网状内皮系统（包括肝脏和脾脏）中被吞噬，这需要进一步研究。此外，由于这些复合物的分子大小较大，它们不会穿过血脑屏障，这表明它们可能相对安全。此外，这些复合物在HNE-1肿瘤中介导DOC浓度升高、血液循环延长和EGFP表达。这些结果提示CD-PLLD/DOC/MMP-9在鼻咽癌治疗中的潜在应用前景。
The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized star-shaped co-polymer consisting of beta-cyclodextrin (CD) and a poly(L-lysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP-9) small interfering RNA, via CD-PLLD/DOC/MMP-9 complexes, into mice implanted with HNE-1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic co-polymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CD-PLLD/DOC/MMP-9 inhibited HNE-1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP-9 was investigated; CD-PLLD/DOC/MMP-9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the blood-brain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE-1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.