Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People's Republic of China.
Department of Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People's Republic of China.
Int J Nanomedicine. 2018 Sep 6;13:5113-5126. doi: 10.2147/IJN.S170862. eCollection 2018.
Effective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance.
Herein, we developed a hyaluronic acid (HA)-modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was done to recognize overexpressed CD44 receptors on GC cells and mediate selective tumor targeting. In parallel, quercetin delivery decreased the expression of Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed multidrug resistance to facilitate DOX activity.
Experimental results demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability and sustained release property. In vitro cell experiments on SGC7901/ADR cells showed selective uptake and increased DOX retention as compared to the DOX mono-delivery system (HA-SiLN/D).
In vivo anticancer assays on the SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).
有效的胃癌（GC）化疗受到许多体外和体内障碍的影响，例如肿瘤微环境和多药耐药性。
本文中，我们开发了一种透明质酸（HA）修饰的硅纳米粒子（HA-SiLN/QD）共递送槲皮素和阿霉素（DOX），以增强 GC 治疗的效果（HA-SiLN/QD）。HA 修饰用于识别 GC 细胞上过表达的 CD44 受体，并介导选择性肿瘤靶向。同时，槲皮素的递送降低了 Wnt16 和 P-糖蛋白的表达，从而重塑肿瘤微环境并逆转多药耐药性以促进 DOX 的活性。
实验结果表明，HA-SiLN/QD 是具有良好稳定性和持续释放性能的纳米级颗粒。与 DOX 单载药系统（HA-SiLN/D）相比，SGC7901/ADR 细胞体外细胞实验显示出选择性摄取和增加的 DOX 保留。
在 SGC7901/ADR 荷瘤小鼠模型中的体内抗癌实验也表明，HA-SiLN/QD 比单载药系统（HA-SiLN/Q 和 HA-SiLN/D）具有显著增强的疗效。
