Quantitative control of active targeting of nanocarriers to tumor cells through optimization of folate ligand density
Quantitative control of active targeting of nanocarriers to tumor cells through optimization of folate ligand density
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通过优化叶酸配体密度定量控制纳米载体主动靶向肿瘤细胞
DOI：
10.1016/j.biomaterials.2014.05.091
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发表时间：
2014
期刊：
影响因子：
14
通讯作者：
Zhou Shaobing
中科院分区：
文献类型：
--
作者：
Tang Zhaomin;Li Dan;Sun Huili;Guo Xing;Chen Yuping;Zhou Shaobing
主动靶向递送系统通过利用叶酸（FA）配体在纳米载体和肿瘤细胞上的叶酸受体（FR）之间产生特异性相互作用，在癌症治疗中得到了广泛的研究。然而，目前尚未发表研究 FA 配体的确定密度对纳米载体主动靶向影响的研究。在本研究中，我们将磁引导氧化铁纳米粒子与FA配体结合，调整FA配体密度，然后研究由此产生的对这种双靶向药物递送系统对肿瘤细胞主动靶向能力的影响。我们还优化了药物递送系统的 FA 配体密度，使其能够在体外主动靶向 FR 过表达的肿瘤细胞。普鲁士蓝染色、透射电子显微镜（TEM）和电感耦合等离子体原子发射光谱（ICP-AES）观察细胞半薄切片表明，最佳FA密度为2.3×1018至2.5×1018/克纳米颗粒（（g·NPs）−1）。我们进一步尝试在携带 4T1 的 BALB/c 小鼠上定性和定量地控制药物对肿瘤的主动靶向和递送。正如预期的那样，体内实验结果还表明，磁性纳米颗粒 (MNP) 的 FA 密度可以进行优化，以便更容易通过多价连接与肿瘤细胞结合，并更容易通过 FR 介导的内吞作用内化。我们的研究可以提供一种定量控制纳米载体主动靶向肿瘤细胞以进行癌症治疗的策略。
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 cellsin 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 × 1018to 2.5 × 1018per 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, thein vivoexperimental 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.