College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, China; Functional Food Enginnering & Technology Research Center of Hubei Province, Wuhan, China.
College of Food Science and Technology, Shanghai Ocean University, LinGang New City, Shanghai, 201306, China.
Colloids Surf B Biointerfaces. 2017 Aug 1;156:19-28. doi: 10.1016/j.colsurfb.2017.05.004. Epub 2017 May 2.
In this study, well-defined folate (FA)-functionalized low density lipoproteins (LDL)/sodium carboxymethyl cellulose (CMC) nanoparticles (NP) were first formulated, utilized in tumor targeting and pH-triggered drug release. CMC was modified with FA before the preparation of NP. A model anti-tumor drug, doxorubicin (DOX), was effectively loaded into the LDL/CMC-FA NP by ionic bonding and hydrophobic interactions. To enhance non-covalent encapsulation stability, self-assembly of DOX-loaded LDL/CMC-FA NP (NP-DOX) was cross-linked by multivalent cations such as Ca (Ca-NP-DOX). The active targeting efficiency of NP-DOX and Ca-NP-DOX was tested against KB cells (FA-receptor over-expressing cells, FR+) and A549 cells (FA-receptor negative-expressing cells, FR-), using FA non-modified DOX-loaded LDL/CMC NP (NG-DOX) as control. The competition assay proved that free FA molecules prevented the cellular uptake of the NP by competitive binding to the FA receptors on the surface of KB cells. This new pH-responsive and FA-targeted nanocarrier may be a promising efficient drug delivery system for potential cancer therapy.
在这项研究中，首先制备了具有明确结构的叶酸（FA）功能化的低密度脂蛋白（LDL）/羧甲基纤维素钠（CMC）纳米颗粒（NP），用于肿瘤靶向和 pH 触发的药物释放。在制备 NP 之前，将 CMC 进行 FA 修饰。通过离子键合和疏水相互作用，将模型抗肿瘤药物阿霉素（DOX）有效负载到 LDL/CMC-FA NP 中。为了增强非共价包封稳定性，通过多价阳离子（如 Ca）交联 DOX 负载的 LDL/CMC-FA NP（NP-DOX）的自组装。使用 FA 未修饰的 DOX 负载的 LDL/CMC NP（NG-DOX）作为对照，对 NP-DOX 和 Ca-NP-DOX 对 KB 细胞（FA 受体过表达细胞，FR+）和 A549 细胞（FA 受体阴性表达细胞，FR-）的主动靶向效率进行了测试。竞争实验证明，游离的 FA 分子通过与 KB 细胞表面的 FA 受体竞争性结合，阻止了 NP 的细胞摄取。这种新的 pH 响应型和 FA 靶向纳米载体可能是一种很有前途的高效药物传递系统，有望用于癌症治疗。
