Abstract

Glioma is the most common malignant tumor of the brain and enhancing the efficacy of chemotherapy in glioma is critical for improving patients’ prognosis. In this study, a glioma-targeting drug delivery system is constructed using biodegradable periodic mesoporous organosilica nanoparticles (PMO) that are modified with lactoferrin (Lf) ligands. The obtained PMO is doped with thioether groups and can be degraded in the high concentration of glutathione in tumor cells. The surface area and pore volume of PMO are 772 cm²/g and 0.98 cm³/g, respectively and the loading capacity of doxorubicin (Dox) is as high as 20%. The results of the confocal laser scanning microscope show that the uptake of PMO-Lf@Dox by C6 cells is higher than PMO@Dox. The quantitative analysis of the flow cytometer further demonstrates that more PMO-Lf@Dox enter C6 cells, indicating that the modification of lactoferrin can significantly increase the uptake of C6 cells. Finally, the therapeutic efficacy results show that Lf-modified PMO enhances the inhibitory effect of Dox on C6 cells when incubated for 24 h and 72 h. In summary, this lactoferrin receptor-mediated PMO drug carrier with biodegradability in glutathione in tumor cells can be used to enhance drug delivery into glioma without long-term accumulation in vivo.

Graphical abstract

中文翻译：

---

通过化疗药物的靶向递送增强可生物降解的周期性介孔有机二氧化硅纳米粒子的抗神经胶质瘤功效

摘要

胶质瘤是最常见的脑部恶性肿瘤，提高胶质瘤化疗的疗效对于改善患者的预后至关重要。在这项研究中，使用乳铁蛋白（Lf）配体修饰的可生物降解的周期性介孔有机二氧化硅纳米颗粒（PMO）构建了一种神经胶质瘤靶向药物递送系统。所得PMO掺杂有硫醚基团，可在肿瘤细胞高浓度的谷胱甘肽中被降解。PMO的表面积和孔容分别为772 cm ² /g和0.98 cm ³ /g，对阿霉素(Dox)的负载量高达20%。共焦激光扫描显微镜结果显示，C6细胞对PMO-Lf@Dox的摄取量高于PMO@Dox。流式细胞仪定量分析进一步表明更多的PMO-Lf@Dox进入C6细胞，说明乳铁蛋白的修饰可以显着增加C6细胞的摄取。最后，疗效结果表明，Lf修饰的PMO在孵育24 h和72 h时增强了Dox对C6细胞的抑制作用。综上所述，这种乳铁蛋白受体介导的PMO药物载体在肿瘤细胞中具有谷胱甘肽的生物降解性，可用于增强药物向神经胶质瘤的递送，而无需在体内长期积累。

图形概要