Department of Biomedical Engineering, University of Virginia School of Engineering and Applied Sciences, PO Box 800759, Health System, Charlottesville, VA 22908, USA.
Integr Biol (Camb). 2013 Jan;5(1):29-42. doi: 10.1039/c2ib20047c.
The way we view cancer has advanced greatly in the past few decades from simplistic approaches to finely honed systems. This transition has been made possible because of advancements on two fronts: the first is the rapidly expanding knowledge base of the mechanisms and characteristics of cancer; the second is innovation in imaging agent design. Rapid advancements in imaging and therapeutic agents are being made through the evolution from one-dimensional molecules to multi-functional nanoparticles. Powerful new agents that have high specificity and minimal toxicity are being developed for in vivo imaging. Here we detail the unique characteristics of cancer that allow differentiation from normal tissue and how they are exploited in nanoparticle imaging development. Firstly, genetic alterations, either endogenous or induced through gene therapy, are one such class of characteristics. Proteomic differences such as overexpressed surface receptors is another targetable feature used for enhanced nanoparticle retention. Increased need for nutrients and specific growth signals to sustain proliferation and angiogenesis are further examples of how cancer can be targeted. Lastly, migration and invasion through a unique microenvironment are two additional traits that are exploitable, due to differences in metalloproteinase concentrations and other factors. These differences are guiding current nanoparticle design to better target, image and treat cancer.
在过去的几十年中，我们对癌症的看法已经从简单的方法发展到了精细的系统。这种转变之所以成为可能，是因为两个方面的进展：一是癌症机制和特征的知识库迅速扩大；二是成像剂设计的创新。通过从一维分子向多功能纳米粒子的演变，成像和治疗剂正在迅速发展。强大的新试剂具有高特异性和最小毒性，正在为体内成像开发。在这里，我们详细介绍了癌症的独特特征，这些特征可与正常组织区分开来，以及如何在纳米粒子成像开发中利用这些特征。首先，基因改变，无论是内源性的还是通过基因治疗诱导的，是这样一类特征。蛋白质组学差异，如过表达的表面受体，是另一个可靶向的特征，用于增强纳米粒子的保留。为了维持增殖和血管生成，癌症需要更多的营养物质和特定的生长信号，这是癌症的另一个靶向目标。最后，通过独特的微环境迁移和入侵是两个额外的可利用的特征，这是由于金属蛋白酶浓度和其他因素的差异。这些差异正在指导当前的纳米粒子设计，以更好地靶向、成像和治疗癌症。
