Karathanasis Efstathios, Park Jaekeun, Agarwal Abhiruchi, Patel Vijal, Zhao Fuqiang, Annapragada Ananth V, Hu Xiaoping, Bellamkonda Ravi V
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
Nanotechnology. 2008 Aug 6;19(31):315101. doi: 10.1088/0957-4484/19/31/315101. Epub 2008 Jun 17.
Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.
纳米载体介导的胶质瘤治疗已显示出前景。基于纳米载体的全身化疗的成功关键取决于所谓的渗漏血管，以允许药物穿过血脑屏障渗出。然而，单个肿瘤中血管通透性的程度差异很大，导致对该治疗的反应范围相应地很广。然而，目前还没有工具能够以个体化、针对患者的方式合理确定肿瘤血管是否适合纳米载体介导的治疗。为了满足脑肿瘤治疗的这一需求，我们开发了一种多功能的100纳米级脂质体试剂，其包裹了一种基于钆的造影剂，用于具有延长血液循环时间的对比增强磁共振成像。使用9.4T MRI系统，由于包裹在纳米载体中的造影剂的磁性能得到改善，我们能够在大鼠胶质瘤模型中追踪负载钆的纳米载体在肿瘤内的分布长达三天。这样的纳米载体提供了一种工具，用于非侵入性评估肿瘤对纳米载体介导治疗的适用性，然后为每个个体肿瘤优化治疗方案。此外，以高分辨率对肿瘤进行成像的能力可能构成肿瘤切除的手术规划工具。
