Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
Department of Pharmacology, Jiangxi Institute of Materia Medica, Nanchang, Jiangxi 330029, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1383-1388. doi: 10.3892/mmr.2017.6715. Epub 2017 Jun 7.
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 β‑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.
载药和载基因的联合递送已成为癌症治疗的主要策略。基于我们之前的研究,一种由β-环糊精(CD)和聚(L-赖氨酸)树枝状大分子(PLLD)组成的星形共聚物被用于通过 CD-PLLD/DOC/MMP-9 复合物共递送多西他赛(DOC)和基质金属蛋白酶 9(MMP-9)小干扰 RNA,进入体内植入 HNE-1 人鼻咽癌(NPC)肿瘤细胞的小鼠体内。与常用的两亲性共聚物胶束不同,所得 CD 衍生物可直接用于核酸和疏水性 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 肿瘤的生长并降低了增殖细胞核抗原的表达水平,为 NPC 治疗提供了一种潜在的策略。此外,还研究了 DOC 和 MMP-9 的分布;CD-PLLD/DOC/MMP-9 复合物被网状内皮系统(包括肝和脾)吞噬,这需要进一步研究。此外,由于其较大的分子尺寸,复合物不能穿过血脑屏障,提示它们可能相对安全。此外,复合物介导的多西他赛浓度增加,血液循环时间延长,在 HNE-1 肿瘤中的 EGFP 表达增加。这些结果表明 CD-PLLD/DOC/MMP-9 复合物在 NPC 治疗中的未来潜在应用。