Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, PR China.
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, PR China.
Int J Biol Macromol. 2024 Mar;261(Pt 2):129726. doi: 10.1016/j.ijbiomac.2024.129726. Epub 2024 Jan 28.
Paclitaxel (PTX) is commonly used in clinical tumor therapy. However, chemoresistance and the inducement of tumor metastasis severely affect the efficacy of PTX. To develop a treatment strategy to reverse chemoresistance, the co-delivery of PTX and small interfering RNA with nanocarriers were programmed in this study. The carrier we have programmed exhibits excellent safety, stability, and delivery efficiency for co-delivery of siRNA and PTX. After rapid release of siRNA, PTX could be released within 72 h. The siBcl-xL and siMcl-1 inhibited cell migration decreased the mitochondrial membrane potential, and induced the release of reactive oxygen species while synergistically functioning with the antineoplastic effects of PTX. Our strategy reduced IC values by 2-5-fold in different cell lines, and the results of flow cytometry confirmed increased apoptosis rates and effectively inhibited cell migration. Synergistic therapy effectively reversed chemoresistance in PTX-resistant breast cancer cells. Similarly, the synergistic administration strategy showed significant sensitizing effects in vivo. Our study demonstrates the combined application of multiple synergistic antitumor administration strategies.
紫杉醇（PTX）常用于临床肿瘤治疗。然而，化疗耐药性和肿瘤转移的诱导严重影响了 PTX 的疗效。为了开发逆转化疗耐药性的治疗策略，本研究设计了用纳米载体共递紫杉醇和小干扰 RNA。我们设计的载体表现出优异的安全性、稳定性和共递 siRNA 和 PTX 的递送效率。siRNA 快速释放后，PTX 可在 72 小时内释放。siBcl-xL 和 siMcl-1 抑制细胞迁移，降低线粒体膜电位，并诱导活性氧的释放，同时与 PTX 的抗肿瘤作用协同。我们的策略使不同细胞系的 IC 值降低了 2-5 倍，流式细胞术的结果证实了细胞凋亡率的增加，并有效抑制了细胞迁移。协同治疗有效逆转了 PTX 耐药乳腺癌细胞的耐药性。同样，协同给药策略在体内显示出显著的增敏作用。本研究证明了多种协同抗肿瘤给药策略的联合应用。
