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Nanoparticle-neural stem cells for targeted ovarian cancer treatment: Optimization of silica nanoparticles for efficient drug loading

机译：用于靶向卵巢癌治疗的纳米粒子-神经干细胞：二氧化硅纳米粒子的优化，可有效负载药物

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One of the drugs used to treat ovarian cancer is cisplatin. However, cisplatin kills normal surrounding tissue in addition to cancer cells. To improve tumor targeting efficiency, our lab uses neural stem cells (NSCs), which migrate directly to ovarian tumors. If free cisplatin is loaded into NSCs for targeted drug delivery, it will kill the NSCs. To prevent the drug cisplatin from killing both the NSCs and normal surrounding tissue, our lab synthesizes silica nanoparticles (SiNPs) that act as a protective carrier. The big picture here is to maximize efficiency of tumor targeting using NSCs and minimize toxicity to these NSCs using SiNPs. The goal of this project is to optimize the stability of SiNPs, which is important for efficient drug loading. To do this, the concentration of tetraethyl orthosilicate (TEOS), one of the main components of SiNPs, was varied. We hypothesized that more TEOS equates to more stable SiNPs because TEOS contributes carbon to SiNPs, and thus a tightly-packed chemical structure results in a stable particle. Then, the stability of the SiNPs were checked in cell media and phosphate buffered saline (PBS). Lastly, the SiNPs were analyzed for their porosity using the transmission electron microscope (TEM). TEM imaging showed white spots in the 200-800 uL TEOS batches and no white spots in the 1000-1800 uL TEOS batches. The white spots were pores, which indicate instability. We concluded that the ultimate factor that determines the stability of SiNPs (100 nm) is the concentration of organic substance.
机译：用于治疗卵巢癌的药物之一是顺铂。然而，顺铂除杀死癌细胞外还杀死正常的周围组织。为了提高肿瘤靶向效率，我们的实验室使用了神经干细胞（NSC），它们直接迁移到卵巢肿瘤。如果将游离顺铂加载到NSC中以进行靶向药物递送，它将杀死NSC。为了防止药物顺铂杀死NSC和正常的周围组织，我们的实验室合成了作为保护性载体的二氧化硅纳米粒子（SiNP）。这里的大图景是使用NSC最大化肿瘤靶向的效率，并使用SiNPs最小化对这些NSC的毒性。该项目的目标是优化SiNP的稳定性，这对于有效载药很重要。为此，改变了SiNPs的主要成分之一的原硅酸四乙酯（TEOS）的浓度。我们假设更多的TEOS等同于更稳定的SiNP，因为TEOS会为SiNPs贡献碳，因此紧密堆积的化学结构会产生稳定的颗粒。然后，在细胞培养基和磷酸盐缓冲液（PBS）中检查了SiNP的稳定性。最后，使用透射电子显微镜（TEM）分析了SiNPs的孔隙率。 TEM成像显示200-800 uL TEOS批次中有白色斑点，而1000-1800 uL TEOS批次中没有白色斑点。白色斑点是毛孔，表明不稳定。我们得出结论，决定SiNPs（100 nm）稳定性的最终因素是有机物质的浓度。

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