Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Key Laboratory of Advanced Technologies of Material, Minister of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Biomaterials. 2014 Sep;35(27):8015-27. doi: 10.1016/j.biomaterials.2014.05.091. Epub 2014 Jun 16.
The active targeting delivery system has been widely studied in cancer therapy by utilizing folate (FA) ligands to generate specific interaction between nanocarriers and folate receptors (FRs) on tumor cell. However, there is little work that has been published to investigate the influence of the definite density of the FA ligands on the active targeting of nanocarriers. In this study, we have combined magnetic-guided iron oxide nanoparticles with FA ligands, adjusted the FA ligand density and then studied the resulting effects on the active targeting ability of this dual-targeting drug delivery system to tumor cells. We have also optimized the FA ligand density of the drug delivery system for their active targeting to FR-overexpressing tumor cells in vitro. Prussian blue staining, semi-thin section of cells observed with transmission electron microscopy (TEM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) have shown that the optimal FA density is from 2.3 × 10(18) to 2.5 × 10(18) per gram nanoparticles ((g·NPs)(-1)). We have further tried to qualitatively and quantitatively control the active targeting and delivering of drugs to tumors on 4T1-bearing BALB/c mice. As expected, the in vivo experimental results have also demonstrated that the FA density of the magnetic nanoparticles (MNPs) could be optimized for a more easily binding to tumor cells via the multivalent linkages and more readily internalization through the FR-mediated endocytosis. Our study can provide a strategy to quantitatively control the active targeting of nanocarriers to tumor cells for cancer therapy.
主动靶向递药系统通过利用叶酸（FA）配体与肿瘤细胞上的叶酸受体（FR）产生特异性相互作用，已在癌症治疗中得到广泛研究。然而，很少有研究报道探讨 FA 配体的确定密度对纳米载体主动靶向的影响。在本研究中，我们将磁性导向氧化铁纳米颗粒与 FA 配体结合，调整 FA 配体密度，然后研究其对这种双重靶向药物传递系统对肿瘤细胞的主动靶向能力的影响。我们还优化了药物传递系统的 FA 配体密度，以实现其对 FR 过表达肿瘤细胞的主动靶向。普鲁士蓝染色、透射电子显微镜（TEM）观察的细胞半薄切片和电感耦合等离子体原子发射光谱（ICP-AES）表明，最佳 FA 密度为每克纳米颗粒（g·NPs）（-1）从 2.3×10(18)到 2.5×10(18)。我们进一步尝试定性和定量控制载有 4T1 的 BALB/c 小鼠的肿瘤的药物主动靶向和递药。不出所料，体内实验结果也表明，通过多价连接，FA 密度可以优化磁性纳米颗粒（MNPs）更容易与肿瘤细胞结合，通过 FR 介导的内吞作用更容易内化。我们的研究可以为定量控制纳米载体对肿瘤细胞的主动靶向提供一种策略，以用于癌症治疗。
