Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Molecules. 2021 Oct 6;26(19):6050. doi: 10.3390/molecules26196050.
Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
胶质母细胞瘤(GB)是一种致命且侵袭性的中枢神经系统癌症。即使进行广泛的切除和放化疗,患者的生存时间仍只有 15 个月。为了维持生长和增殖,癌细胞需要高度的氧化状态。姜黄素是一种众所周知的抗炎抗氧化剂,是治疗 GB 的潜在候选药物。为了促进治疗剂量的姜黄素有效递送至细胞内,我们将药物包裹在表面修饰的聚酰胺胺(PAMAM)树枝状大分子中。我们研究了传统的 PAMAM 树枝状大分子(100%胺表面,G4 NH)、表面修饰的树枝状大分子(10%胺和 90%羟基-G4 90/10-Cys)和包裹姜黄素的树枝状大分子(G4 90/10-Cys-Cur)对三种胶质母细胞瘤细胞系:小鼠-GL261、大鼠-F98 和人-U87 的效果。通过 MTT 法检测细胞活力,我们发现与非癌细胞对照相比,G4 90/10-Cys-Cur 降低了所有三种胶质母细胞瘤细胞系的活力。在类似的条件下,未包裹的姜黄素没有效果,而未修饰的树枝状大分子(G4 NH)导致癌细胞和正常细胞的大量死亡。通过利用和优化 PAMAM 树枝状大分子的成分,我们为递送达癌治疗药物提供了一种有前景的新途径。我们用姜黄素得到的结果表明,抗氧化剂是治疗胶质母细胞瘤的良好候选药物。