School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
Carbohydr Polym. 2015 May 20;122:26-38. doi: 10.1016/j.carbpol.2014.12.061. Epub 2015 Jan 5.
The aim of our study is to develop a new function of low molecular weight heparin (LMWHEP) for targeting tumor metastatic lymph node based on LMWHEP-modified nanoliposome and LMWHEP-heparanase (HPA) interaction (LMWHEP-HPA). At First, LMWHEP-modified nanoliposomes (LMWHEP-LPs) were prepared by the electrostatic attraction and the physiochemical properties were evaluated. Then the effects of LMWHEP-HPA on the stability and drug release were investigated. In addition, the cellular uptake of LMWHEP-LPs was studied by using Hela, MCF-7, L929 and RAW264.7 cells. Finally, the targeting ability as well as the tissue distribution was examined in the mice model bearing Hela tumor lymph node metastasis. LMWHEP-LPs prepared had suitable physicochemical properties. The effect results of LMWHEP-HPA showed that LMWHEP coated on the surface of nanoliposome could be degraded by HPA. Compared with the unmodified-nanoliposome, the LMWHEP modification could improve the cellular uptake and increase the targeting ability to the metastatic lymph nodes according to LMWHEP-HPA. This study demonstrates LMWHEP is a highly promising polymer material for the targeting of tumor lymph node metastasis.
本研究旨在基于低分子肝素（LMWHEP）修饰的纳米脂质体和 LMWHEP-肝素酶（HPA）相互作用（LMWHEP-HPA），开发 LMWHEP 靶向肿瘤转移淋巴结的新功能。首先，通过静电吸引制备了 LMWHEP 修饰的纳米脂质体（LMWHEP-LPs），并评价了其理化性质。然后考察了 LMWHEP-HPA 对稳定性和药物释放的影响。此外，采用 Hela、MCF-7、L929 和 RAW264.7 细胞研究了 LMWHEP-LPs 的细胞摄取。最后，在荷瘤 Hela 肿瘤淋巴结转移的小鼠模型中，考察了 LMWHEP-LPs 的靶向能力和组织分布。制备的 LMWHEP-LPs 具有适宜的理化性质。LMWHEP-HPA 的作用结果表明，HPA 可降解表面涂覆 LMWHEP 的纳米脂质体。与未修饰的纳米脂质体相比，LMWHEP 修饰可通过 LMWHEP-HPA 提高细胞摄取并增加对转移淋巴结的靶向能力。本研究表明，LMWHEP 是一种很有前途的聚合物材料，可用于靶向肿瘤淋巴结转移。
