van Solinge Thomas S, Friis Kristina Pagh, O'Brien Killian, Verschoor Romy L, van Aarle Jeroen, Koekman Arnold, Breakefield Xandra O, Vader Pieter, Schiffelers Raymond, Broekman Marike
Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA.
Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands.
Int J Pharm X. 2023 Jun 21;6:100191. doi: 10.1016/j.ijpx.2023.100191. eCollection 2023 Dec 15.
In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma Cy5.5 labeled liposomes could be detected with imaging after direct intra-tumoral injection. analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.
在胶质母细胞瘤（一种恶性原发性脑肿瘤）中，脂质体在临床前和早期临床试验中已显示出作为治疗药物递送载体的潜力。然而，影响胶质瘤细胞对脂质体细胞摄取的外部因素尚不清楚。肝素和肝素类似物常用于胶质瘤患者以降低血栓栓塞事件的风险。我们的结果表明，肝素以剂量依赖性方式抑制U87胶质瘤细胞和GL261细胞对聚乙二醇化脂质体的摄取，并且肝素介导的摄取抑制需要培养基中存在胎牛血清。在胶质瘤皮下模型中，直接瘤内注射后通过成像可检测到Cy5.5标记的脂质体。流式细胞术分析显示，与仅用赋形剂处理的小鼠相比，全身用肝素处理的小鼠肿瘤细胞对脂质体的摄取减少。
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