Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, Taiwan, Republic of China.
Int J Nanomedicine. 2018 May 22;13:3011-3026. doi: 10.2147/IJN.S161314. eCollection 2018.
Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy.
In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added.
With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment.
The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.
将大型药物纳米载体深入渗透到肿瘤中对于提高肿瘤治疗效果很重要。
在这项研究中，我们开发了一种由载紫杉醇（PTX）的希腊士兵（GS；~20nm）组装在具有亲水性洛沙坦（LST）的两亲性明胶基质中组成的尺寸可变化的“特洛伊木马”纳米载体（THNC）。
通过基质金属蛋白酶-2裂解两亲性明胶基质，LST 在 6 小时内快速释放高达 60%的累积药物，但从 GS 中检测到 PTX 的缓慢释放动力学（~20%），表明 THNC 能够控制 LST 和 PTX 药物的释放以渗透到肿瘤组织中。在 3D 肿瘤球体模型中的体外细胞活力研究表明，从 THNC 中释放的载有 PTX 的 GS 表现出更深的渗透和更高的细胞毒性，将肿瘤球体缩小到原来大小的一半，并破坏肿瘤微环境的结构。
结果表明，具有控制药物释放和磁性 GS 深入渗透的 THNC 显示出癌症治疗的巨大潜力。
