A transistor-like pH nanoprobe for tumour detection and image-guided surgery

Abstract

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 mm3) 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.

Optical molecular imaging for tumor detection and image-guided surgery

“…7A). The resulting nanosensor was not only able to detect a broad range of tumors in mouse models, but also to enable real-time image-guided resection of established tumors and occult nodules [20]. By using a clinical SPY™ Elite camera, ICG-UPS can achieve high tumor over normal tissue ratio (>20) in a wide variety of tumor models (Fig.…”

“…Adapted from Ref. [20]with permissions. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.…”

“…prostate-specific membrane antigen, PSMA) [17], carcinoembryonic antigen and carbohydrate antigen 19–9 (CA19–9) [18,19]. In addition, aberrant metabolism is also a hallmark of cancer cells, which cultivates a unique tumor metabolic microenvironment with dysregulated extra and intra-cellular pH [20], hypoxia [21] and increased secretion of proteases (e.g. matrix metalloproteinases, cathepsins [22,23] and γ-glutamyltranspeptidase [24]) which are all potential cancer specific targets as well.…”

In Situ Monitoring of MicroRNA Replacement Efficacy and Accurate Imaging‐Guided Cancer Therapy through Light‐Up Inter‐Polyelectrolyte Nanocomplexes

“…However, it should be mentioned that conventional “always on” theranostics are defective because fluorescence signals are emitted regardless of their real location in the focal zone and as a result displaying poor signal‐to‐noise ratio (S/N ratio) or even “false positive” results 13. To address this issue, reversibly activatable light‐up nanoprobes are of great need to be developed to emit signals from “off‐state” to “on‐state” in the site of interest to improve S/N ratio 14, 15, 16, 17, 18. Moreover, such platforms provide great potential to be used for real‐time monitoring of the transportation and release of “drug/gene” in tumor cells and tumor tissues 19.…”

Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer

“…As new technologies such as image-guided surgery become increasingly common, 25,26 we can continue to anticipate improvements in oncologic and functional outcomes for HNSCC patients. Just as significant is the larger ongoing effort to better match treatment intensity to a disease that is now epidemiologically better defined.…”