Zhao Tian, Huang Gang, Li Yang, Yang Shunchun, Ramezani Saleh, Lin Zhiqiang, Wang Yiguang, Ma Xinpeng, Zeng Zhiqun, Luo Min, de Boer Esther, Xie Xian-Jin, Thibodeaux Joel, Brekken Rolf A, Sun Xiankai, Sumer Baran D, Gao Jinming
Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA.
Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA.
Nat Biomed Eng. 2016;1. doi: 10.1038/s41551-016-0006. Epub 2016 Dec 19.
Because of profound genetic and histological differences in cancerous tissue, it is challenging to detect a broad range of malignant tumours at high resolution. Here, we report the design and performance of a fluorescent nanoprobe with transistor-like responses (transition pH = 6.9) for the detection of the deregulated pH that drives many of the invasive properties of cancer. The nanoprobe amplifies fluorescence signal in the tumour over that in the surrounding normal tissues, resulting in a discretized, binary output signal with spatial resolution smaller than 1 mm. The nanoprobe allowed us to image a broad range of tumours in mouse models using a variety of clinical cameras, and to perform real-time tumour-acidosis-guided detection and surgery of occult nodules (< 1 mm) in mice bearing head-and-neck or breast tumours, significantly lengthening mice survivability. We also show that the pH nanoprobe can be used as a reporter in a fast, quantitative assay to screen for tumour-acidosis inhibitors. The binary delineation of pH achieved by the nanoprobe promises to improve the accuracy of cancer detection, surveillance and therapy.
由于癌组织在基因和组织学上存在显著差异，要在高分辨率下检测多种恶性肿瘤具有挑战性。在此，我们报告了一种具有类似晶体管响应（转变pH = 6.9）的荧光纳米探针的设计与性能，用于检测驱动癌症许多侵袭性特征的失调pH值。该纳米探针在肿瘤中的荧光信号比周围正常组织中的更强，从而产生空间分辨率小于1毫米的离散二元输出信号。该纳米探针使我们能够使用各种临床相机对小鼠模型中的多种肿瘤进行成像，并对患有头颈或乳腺肿瘤的小鼠进行实时肿瘤酸中毒引导的隐匿结节（<1毫米）检测和手术，显著延长了小鼠的生存期。我们还表明，pH纳米探针可用作快速定量检测中筛选肿瘤酸中毒抑制剂的报告分子。该纳米探针实现的pH二元描绘有望提高癌症检测、监测和治疗的准确性。
