Semiconducting Polymer Nanospherical Nucleic Acid Probe for Transcriptomic Imaging of Cancer Chemo-Immunotherapy.

Real-time in vivo imaging of RNA can enhance our understanding of physio-pathological processes. However, most nucleic acid-based sensors have poor resistance to nucleases and limited photophysical properties, making them suboptimal for this purpose. To address this, we have developed a semiconducting polymer nanospherical nucleic acid probe (SENSE) for transcriptomic imaging of cancer immunity in living mice. SENSE consists of a semiconducting polymer backbone covalently linked with a recognition DNA strand, which is complemented by a dye-labelled signal DNA strand. Upon detection of a targeted T lymphocyte transcript (Gzmb: granzyme B), the signal strand is released from SENSE, leading to a fluorescence enhancement of the signal dye and superb sensitivity for signal correlation with transcript levels. The always-on fluorescence of the SP core in SENSE also serves as an internal reference for tracking SENSE uptake in tumours. Thus, SENSE has the du-al-signal channel that allows for ratiometric imaging of Gzmb transcripts in the tumour of living mice for evaluating chemo-immunotherapy; moreover, it has demonstrated sensitivity and specificity comparable to flow cytometry and qPCR, with the added benefit of a faster and simpler means of T cell detection in resected tumours. Therefore, SENSE represents a promising tool for in vivo RNA imaging. This article is protected by copyright. All rights reserved.