Quantitative Imaging of MicroRNA-21 In Vivo for Real-Time Monitoring of the Cancer Initiation and Progression

MicroRNA-21 (MiR-21) has been confirmed to be upregulated in tumors, and its abnormal expression is closely associated with tumor occurrence. However, the traditional imaging methods are limited to qualitative imaging of miR-21, and no effective strategy has been developed for monitoring its concentration in vivo during cancer initiation and progression. Herein, a biosensor is created utilizing a NIR-II ratiometric fluorescent nanoprobe to quantitatively monitor dynamic alterations in miR-21 levels in vivo. The nanoprobe (termed DCNP@DNA2@IR806) is constructed by introducing IR806 as a donor and down-conversion nanoparticles (DCNP) as the acceptor, using DNA as linkers. Upon miR-21-responsive initiation of the nanoprobe, the 1550 nm fluorescent signal of DCNP stimulated by a 808 nm laser (F1550, 808Ex) increased because of the close proximity of IR806 to the DCNP and the subsequent non-radiative energy transfer (NRET). Meanwhile, the 1550 nm fluorescent signal of DCNP stimulated by a 980 nm laser (F1550, 980Ex) remained stable because of the absence of NRET. This ratiometric NIR-II fluorescent signal has been confirmed to be a reliable indicator of miR-21 concentration in vivo. The strategy holds promise for further enhancing the understanding of microRNAs-based molecular mechanisms underlying cancer progression, laying a foundation for the early diagnosis of microRNAs-related diseases. A miR-21-activated ratiometric NIR-II fluorescence nanoprobe (DCNP@DNA2@IR806) for early diagnosis and real-time monitoring of miR-21 levels during cancer initiation and progression via enhanced ratiometric fluorescence signals in vivo. The content of activated miR-21 is positively correlated with tumor volume in the development of tumors. image