Habra Kinana, McArdle Stéphanie E B, Morris Robert H, Cave Gareth W V
School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK.
John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK.
Nanomaterials (Basel). 2021 Aug 24;11(9):2157. doi: 10.3390/nano11092157.
The complete removal of glioblastoma brain tumours is impossible to achieve by surgery alone due to the complex finger-like tentacle structure of the tumour cells and their migration away from the bulk of the tumour at the time of surgery; furthermore, despite aggressive chemotherapy and radiotherapy treatments following surgery, tumour cells continue to grow, leading to the death of patients within 15 months after diagnosis. The naturally occurring carnosine dipeptide has previously demonstrated activity against in vitro cultured glioblastoma cells; however, at natural physiological concentrations, its activity is too low to have a significant effect. Towards realising the full oncological potential of carnosine, the dipeptide was embedded within an externally triggered carrier, comprising a novel nano rod-shaped superparamagnetic iron oxide nanoparticle (ca. 86 × 19 × 11 nm) capped with a branched polyethyleneimine, which released the therapeutic agent in the presence of an external magnetic field. The new nano-carrier was characterized using electron microscopy, dynamic light scattering, elemental analysis, and magnetic resonance imaging techniques. In addition to cytotoxicity studies, the carnosine carrier's effectiveness as a treatment for glioblastoma was screened in vitro using the U87 human glioblastoma astrocytoma cell line. The labile carnosine (100 mM) suppresses both the U87 cells' proliferation and mobility over 48 h, resulting in significant reduction in migration and potential metastasis. Carnosine was found to be fully released from the carrier using only mild hyperthermia conditions (40 °C), facilitating an achievable clinical application of the slow, sustained-release treatment of glioblastoma brain tumours that demonstrates potential to inhibit post-surgery metastasis with the added benefit of non-invasive monitoring via MRI.
由于胶质母细胞瘤脑肿瘤细胞具有复杂的指状触手结构，且在手术时会从肿瘤主体迁移出去，仅通过手术无法完全切除这些肿瘤；此外，尽管术后进行了积极的化疗和放疗，但肿瘤细胞仍继续生长，导致患者在诊断后15个月内死亡。天然存在的肌肽二肽此前已证明对体外培养的胶质母细胞瘤细胞具有活性；然而，在天然生理浓度下，其活性过低，无法产生显著效果。为了充分发挥肌肽的肿瘤学潜力，将该二肽嵌入一个外部触发载体中，该载体由一种新型纳米棒状超顺磁性氧化铁纳米颗粒（约86×19×11纳米）组成，表面覆盖有支化聚乙烯亚胺，可在外部磁场存在时释放治疗剂。使用电子显微镜、动态光散射、元素分析和磁共振成像技术对新型纳米载体进行了表征。除了细胞毒性研究外，还使用U87人胶质母细胞瘤星形细胞瘤细胞系在体外筛选了肌肽载体治疗胶质母细胞瘤的有效性。不稳定的肌肽（100 mM）在48小时内抑制了U87细胞的增殖和迁移，导致迁移和潜在转移显著减少。发现仅在温和的热疗条件（40°C）下，肌肽就能从载体中完全释放出来，这有助于实现胶质母细胞瘤脑肿瘤缓慢、持续释放治疗的临床应用，该治疗方法显示出抑制术后转移的潜力，并具有通过MRI进行无创监测的额外优势。
