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As a post transcriptional regulator of gene expression, microRNAs (miRNA) is closely related to many major human diseases, especially cancer. Therefore, its precise detection is very important for disease diagnosis and treatment. With the advancement of fluorescent dye and imaging technology, the focus has shifted from in vitro miRNA detection to in vivo miRNA imaging. This concept review summarizes signal amplification strategies including DNAzyme catalytic reaction, hybrid chain reaction (HCR), catalytic hairpin assembly (CHA) to enhance detection signal of lowly expressed miRNAs; external stimuli of ultraviolet (UV) light or near‐infrared region (NIR) light, and internal stimuli such as adenosine triphosphate (ATP), glutathione (GSH), protease and cell membrane protein to prevent nonspecific activation for the avoidance of false positive signal; and the development of fluorescent probes with emission in NIR for in vivo miRNA imaging; as well as rare earth nanoparticle based the second near‐infrared window (NIR‐II) nanoprobes with excellent tissue penetration and depth for in vivo miRNA imaging. The concept review also indicated current challenges for in vivo miRNA imaging including the dynamic monitoring of miRNA expression change and simultaneous in vivo imaging of multiple miRNAs. [ABSTRACT FROM AUTHOR]

Aberrant expressions of biomolecules occur much earlier than tumor visualized size and morphology change, but their common measurement strategies such as biopsy suffer from invasive sampling process. In vivo imaging of slight biomolecule expression difference is urgently needed for early cancer detection. Fluorescence of rare earth nanoparticles (RENPs) in second near-infrared (NIR-II) region makes them appropriate tool for in vivo imaging. However, the incapacity to couple with signal amplification strategies, especially programmable signal amplification strategies, limited their application in lowly expressed biomarkers imaging. Here we develop a 980/808 nm NIR programmed in vivo microRNAs (miRNAs) magnifier by conjugating activatable DNAzyme walker set to RENPs, which achieves more effective NIR-II imaging of early stage tumor than size monitoring imaging technique. Dye FD1080 (FD1080) modified substrate DNA quenches NIR-II downconversion emission of RENPs under 808 nm excitation. The miRNA recognition region in DNAzyme walker is sealed by a photo-cleavable strand to avoid "false positive" signal in systemic circulation. Upconversion emission of RENPs under 980 nm irradiation activates DNAzyme walker for miRNA recognition and amplifies NIR-II fluorescence recovery of RENPs via DNAzyme catalytic reaction to achieve in vivo miRNA imaging. This strategy demonstrates good application potential in the field of early cancer detection., (© 2023 Wiley-VCH GmbH.)

Photothermal therapy (PTT) has emerged as one of the important strategies for cancer treatment due to its precision and no drug resistance. However, upregulation of heat shock protein (HSP) expression during PTT severely limits its overall therapeutic effect. Accordingly, in this study, we developed a new anticancer strategy based on an l-glutathione (GSH)-activated prodrug (Cy-S-S-Cbl), which consisted of an alkylating reagent (Cbl) covalently linked to a photothermal photosensitizer (Cy7), to achieve cooperatively enhanced photothermal-chemotherapy. In the presence of overexpressed GSH in cancer cells, Cy-S-S-Cbl was converted into Cy-NH 2 to achieve photothermal effect enhancement by the photo-induced electron transfer (PET) effect and release the alkylation reagent. Meanwhile, the photothermal effect of Cy-NH 2 enhanced the DNA alkylation of chemotherapy drugs. Surprisingly, we first found that the therapeutic efficacy of PTT was improved owing to the down-regulation of heat shock protein 70 (HSP70) by chemotherapy. The two treatments had a synergistic promotion effect achieving higher cancer cell killing efficiency. Under 808 nm light irradiation, Cy-S-S-Cbl could effectively realize selective killing of cancer cells and tumor growth inhibition. Therefore, we strongly believe that this efficient cooperative design strategy will provide a new idea to improve the treatment efficiency of prodrugs., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)