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

Abstract

Real‐time in vivo imaging of RNA can enhance the 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, a semiconducting polymer nanospherical nucleic acid probe (SENSE) for transcriptomic imaging of cancer immunity in living mice is developed. SENSE comprises a semiconducting polymer (SP) backbone covalently linked with recognition DNA strands, which are complemented by dye‐labeled signal DNA strands. Upon detection of targeted T lymphocyte transcript (Gzmb: granzyme B), the signal strands are released, leading to a fluorescence enhancement correlated to transcript levels with superb sensitivity. The always‐on fluorescence of the SP core also serves as an internal reference for tracking SENSE uptake in tumors. Thus, SENSE has the dual‐signal channel that enables ratiometric imaging of Gzmb transcripts in the tumor of living mice for evaluating chemo‐immunotherapy; moreover, it has demonstrated sensitivity and specificity comparable to flow cytometry and quantitative polymerase chain reaction, yet offering a faster and simpler means of T cell detection in resected tumors. Therefore, SENSE represents a promising tool for in vivo RNA imaging.

Organic Semiconducting Sono-Metallo-Detonated Immunobombs for Ultrasensitized Domestication of Immunosuppressive Cells

“…For example, U.S. Food and Drug Administration (FDA)-approved ferumoxytol and coordination complexes of Mn 2+ ions and STING (stimulator of interferon genes) agonists efficiently overcome the disadvantages of free metal ions while promoting M2 (M2 macrophages)-to-M1 (M1 macrophages) polarization of TAMs. Recently, organic semiconducting polymers (SPs), which serve as versatile materials for biosensors, imaging probes, − and drug delivery systems, , have been used to coordinate metals for synergistic photo- and sono-activated , cancer therapy. However, despite their great potential, the direct dynamic bioavailability and mechanism of SPs and metals in the regulation of immunosuppressive cells are still largely unknown, and the systemic development of metal immunotherapy platforms remains a challenge.…”