Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 214122, Wuxi, China.
Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 214062, Wuxi, Jiangsu, China.
Carbohydr Res. 2020 Jul;493:108032. doi: 10.1016/j.carres.2020.108032. Epub 2020 May 12.
Milk exosomes (mExo), similar to cell-derived exosomes, are emerging as promising nanocarriers for delivery of therapeutic molecules such as chemical drugs and siRNA, due to the excellent biocompatibility and low-cost production from bovine milk. However, additional modification remains required to apply milk exosomes for tumor-specific drug delivery. Here, we attempted to develop a novel strategy for directing doxorubicin (Dox)-loaded mExo to CD44-overexpressing tumor cells. Hyaluronan (HA), a CD44-specific ligand, was functionalized with an amphiphilic molecule DSPE-PEG which enabled the spontaneous decoration of Dox-loaded mExo with HA onto the phospholipid bilayer. The obtained nanocarrier HA-mExo-Dox was shown to be able to selectively deliver Dox into cells with over-expressed CD44 instead of control cells and trigger the notable tumor cells death in the in vitro analysis. This study demonstrates the potential use of HA-displaying mExo for tumor cell-specific drug delivery and this strategy should prove to be feasible for targeted cancer therapy.
牛奶外泌体（mExo）与细胞来源的外泌体类似，由于其具有极好的生物相容性和从牛奶低成本生产的优势，正成为递呈治疗分子（如化学药物和 siRNA）的有前途的纳米载体。然而，仍需要进一步的修饰才能将牛奶外泌体应用于肿瘤特异性药物传递。在这里，我们试图开发一种将载多柔比星（Dox）的 mExo 靶向递送至过表达 CD44 的肿瘤细胞的新策略。透明质酸（HA）是 CD44 的特异性配体，与两亲分子 DSPE-PEG 功能化，使 HA 能够自发地将 Dox 负载的 mExo 装饰在磷脂双层上。体外分析表明，所得纳米载体 HA-mExo-Dox 能够选择性地将 Dox 递送至过表达 CD44 的细胞，而不是对照细胞，并引发显著的肿瘤细胞死亡。这项研究证明了 HA 展示 mExo 用于肿瘤细胞特异性药物传递的潜力，并且该策略应该适用于靶向癌症治疗。
