Nandwana Vikas, De Mrinmoy, Chu Shihyao, Jaiswal Manish, Rotz Matt, Meade Thomas J, Dravid Vinayak P
Department of Materials Science and Engineering, Northwestern University, Evanston, USA.
Cancer Treat Res. 2015;166:51-83. doi: 10.1007/978-3-319-16555-4_3.
Despite the complexities of cancer, remarkable diagnostic and therapeutic advances have been made during the past decade, which include improved genetic, molecular, and nanoscale understanding of the disease. Physical science and engineering, and nanotechnology in particular, have contributed to these developments through out-of-the-box ideas and initiatives from perspectives that are far removed from classical biological and medicinal aspects of cancer. Nanostructures, in particular, are being effectively utilized in sensing/diagnostics of cancer while nanoscale carriers are able to deliver therapeutic cargo for timed and controlled release at localized tumor sites. Magnetic nanostructures (MNS) have especially attracted considerable attention of researchers to address cancer diagnostics and therapy. A significant part of the promise of MNS lies in their potential for "theranostic" applications, wherein diagnostics makes use of the enhanced localized contrast in magnetic resonance imaging (MRI) while therapy leverages the ability of MNS to heat under external radio frequency (RF) field for thermal therapy or use of thermal activation for release of therapy cargo. In this chapter, we report some of the key developments in recent years in regard to MNS as potential theranostic carriers. We describe that the r₂relaxivity of MNS can be maximized by allowing water (proton) diffusion in the vicinity of MNS by polyethylene glycol (PEG) anchoring, which also facilitates excellent fluidic stability in various media and extended in vivo circulation while maintaining high r₂values needed for T₂-weighted MRI contrast. Further, the specific absorption rate (SAR) required for thermal activation of MNS can be tailored by controlling composition and size of MNS. Together, emerging MNS show considerable promise to realize theranostic potential. We discuss that properly functionalized MNS can be designed to provide remarkable in vivo stability and accompanying pharmacokinetics exhibit organ localization that can be tailored for specific applications. In this context, even iron-based MNS show extended circulation as well as diverse organ accumulation beyond liver, which otherwise renders MNS potentially toxic to liver function. We believe that MNS, including those based on iron oxides, have entered a renaissance era where intelligent synthesis, functionalization, stabilization, and targeting provide ample evidence for applications in localized cancer theranostics.
尽管癌症情况复杂，但在过去十年中，诊断和治疗方面仍取得了显著进展，其中包括对该疾病在基因、分子和纳米尺度上的认识有所提高。物理科学与工程，尤其是纳米技术，通过跳出框框的想法和举措，从与癌症经典生物学和医学方面相去甚远的角度，为这些进展做出了贡献。特别是，纳米结构正有效地应用于癌症的传感/诊断，而纳米级载体能够在局部肿瘤部位实现治疗药物的定时和控释。磁性纳米结构（MNS）尤其引起了研究人员对癌症诊断和治疗的极大关注。MNS的很大一部分前景在于其在“诊疗一体化”应用中的潜力，其中诊断利用磁共振成像（MRI）中增强的局部对比度，而治疗则利用MNS在外部射频（RF）场下加热以进行热疗的能力，或利用热激活来释放治疗药物。在本章中，我们报告了近年来MNS作为潜在诊疗一体化载体的一些关键进展。我们描述了通过聚乙二醇（PEG）锚固使水（质子）在MNS附近扩散，可以使MNS的r₂弛豫率最大化，这也有助于在各种介质中具有出色的流体稳定性，并延长体内循环时间，同时保持T₂加权MRI对比度所需的高r₂值。此外，通过控制MNS的组成和尺寸，可以调整MNS热激活所需的比吸收率（SAR）。总之，新兴的MNS在实现诊疗一体化潜力方面显示出相当大的前景。我们讨论了可以设计功能化适当的MNS，以提供出色的体内稳定性，并且伴随的药代动力学表现出的器官定位可以针对特定应用进行调整。在这种情况下，即使是铁基MNS也显示出延长的循环时间以及除肝脏外的多种器官积累，否则MNS可能对肝功能有毒性。我们相信，包括基于氧化铁的MNS在内，已经进入了一个复兴时代，智能合成、功能化、稳定化和靶向为局部癌症诊疗一体化应用提供了充分的证据。
