Deep Tissue Translocation of Graphene Oxide Sheets in Human Glioblastoma 3D Spheroids and an Orthotopic Xenograft Model
Deep Tissue Translocation of Graphene Oxide Sheets in Human Glioblastoma 3D Spheroids and an Orthotopic Xenograft Model
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DOI：
10.1002/adtp.202000109
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发表时间：
2020-10-09
影响因子：
4.6
通讯作者：
Kostarelos, Kostas
中科院分区：
文献类型：
--
作者：
de Lazaro, Irene;Sharp, Paul;Kostarelos, Kostas
它的解剖学定位，高度异质性和耐药性的肿瘤细胞群和“冷”免疫微环境，都对胶质母细胞瘤的治疗提出了挑战。纳米级药物递送系统，包括氧化石墨烯（GO）薄片，可以绕过生物屏障，递送多个货物以同时影响几个途径，或靶向免疫区室，从而避免这些问题中的一些。在此，研究了GO薄片与胶质母细胞瘤的体外（U-87 MG三维球状体，没有基质或免疫隔室）和体内（U-87 MG原位异种移植物）模型的相互作用。在体外，GO薄片深深地易位到球状体中，在肿瘤细胞中几乎没有内化。在体内，颅内给药的GO也显示在整个肿瘤中广泛分布，并且在研究期间对肿瘤生长和进展没有影响。肿瘤细胞内的内化也很少，大部分薄片优先被小胶质细胞/巨噬细胞摄取。结果表明，GO薄片可以在整个胶质母细胞瘤肿瘤中提供深度和均匀的分布，并且是靶向其骨髓区室的手段。有必要进一步研究GO薄片在肿瘤块内的运输机制及其递送生物活性货物的能力，但最终，这些信息可以为开发针对胶质母细胞瘤的免疫疗法提供信息。
Its anatomical localization, a highly heterogeneous and drug-resistant tumor cell population and a "cold" immune microenvironment, all challenge the treatment of glioblastoma. Nanoscale drug delivery systems, including graphene oxide (GO) flakes, may circumvent some of these issues bypassing biological barriers, delivering multiple cargoes to impact several pathways simultaneously, or targeting the immune compartment. Here, the interactions of GO flakes with in vitro (U-87 MG three-dimensional spheroids, without stromal or immune compartments) and in vivo (U-87 MG orthotopic xenograft) models of glioblastoma are investigated. In vitro, GO flakes translocated deeply into the spheroids with little internalization in tumor cells. In vivo, intracranially administered GO also show extensive distribution throughout the tumor and demonstrate no impact on tumor growth and progression for the duration of the study. Internalization within tumor cells is also scarce, with the majority of flakes preferentially taken up by microglia/macrophages. The results indicate that GO flakes could offer deep and homogenous distribution throughout glioblastoma tumors and a means to target their myeloid compartment. Further studies are warranted to investigate the mechanisms of GO flakes transport within the tumor mass and their capacity to deliver bioactive cargoes but, ultimately, this information could inform the development of immunotherapies against glioblastoma.