Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
J Control Release. 2014 Nov 28;194:228-37. doi: 10.1016/j.jconrel.2014.09.005. Epub 2014 Sep 16.
A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.
一种能够将癌症相关 microRNAs 和化疗药物递送到肿瘤中特定靶点的共递药系统，是消除肺癌治疗中肿瘤复发的一种有吸引力的策略。在这项研究中，我们开发了一种用于内源性 microRNA（miR-34a）和紫杉醇（PTX）的双重药物递送系统，用于协同癌症治疗。PTX（减数分裂抑制剂）和 miR-34a 被装载到阳离子固体脂质纳米粒（miSLNs-34a/PTX）中，用于治疗转移到小鼠肺部的 B16F10-CD44(+)黑色素瘤。该纳米颗粒系统在血清中对 miR-34a 和 PTX 的降解具有良好的保护作用，通过光子相关光谱（PCS）测定平均粒径约为 220nm。体外实验表明，PTX 和 miR-34a 的并行活性具有协同抗癌功效。体内实验表明，miSLNs-34a/PTX 对荷瘤肺组织具有被动靶向性，与单载药固体脂质纳米粒相比，其抑制 B16F10 荷瘤肿瘤生长和消除肺部癌细胞群体的能力要强得多。结果表明，这种 miR-34a 和 PTX 的共递药系统有希望增强癌症治疗以减少肿瘤复发。
