Nano metal–organic framework (NMOF)-based strategies for multiplexed microRNA detection in solution and living cancer cells

Abstract

MiRNAs are an emerging type of biomarker for diagnostics and prognostics. A reliable sensing strategy that can monitor miRNA expression in living cancer cells would be critical in view of its extensive advantages for fundamental research related to miRNA-associated bioprocesses and biomedical applications. Conventional miRNA sensing methods include northern blot, microarrays and real-time quantitative PCR. However, none of them is able to monitor miRNA levels expressed in living cancer cells in a real-time fashion. Some fluorescennt biosensors developed recently from carbon nanomaterials, such as single-walled carbon nanotubes (SWNTs), graphene oxide (GO), and carbon nanoparticles, have been successfully used for assaying miRNA in vitro; however the preparation processes are often expensive, complicated and time-consuming, which have motivated the research on other substitute and novel materials. Herein we present a novel sensing strategy based on peptide nucleic acid (PNA) probes labeled with fluorophores and conjugated with an NMOF vehicle to monitor multiplexed miRNAs in living cancer cells. The NMOF works as a fluorescence quencher of the labelled PNA that is firmly bound with the metal center. In the presence of a target miRNA, PNA is hybridized and released from the NMOF leading to the recovery of fluorescence. This miRNA sensor not only enables the quantitative and highly specific detection of multiplexed miRNAs in living cancer cells, but it also allows the precise and in situ monitoring of the spatiotemporal changes of miRNA expression.

MicroRNAs in tumor angiogenesis

“…Now abundance variation of many miRNAs in specific tumor have been tested. Wu and his colleagues produced a miRNA sensor, which not only enabled the quantitative and highly specific detection of multiplexed miRNAs in living cancer cells, but also allowed the precise and in situ monitoring of the spatiotemporal changes of miRNA expression (Wu et al , 2015). Moreover, some miRNA expression profiles in cancer cells have been used in the diagnosis of cancer, such as miR-18a and miR-155 (Komatsu et al, 2014, Sochor et al , 2014.…”

MnO2 Nanotube-Based NanoSearchlight for Imaging of Multiple MicroRNAs in Live Cells

“…19 In order to achieve high FRET efficiency, some nanomaterials, particularly 0D and 2D nanomaterials, have been fabricated as nanoquenchers for miRNA detection, including gold nanoparticles, 20 quantum dots, 21 carbon nanoparticles, 22 graphene oxide, 23 WS 2 nanosheets, 24 and metal-organic frameworks. 25 It is worth noting that few 1D nanotubes beyond carbon nanotubes 26–28 have been reported for such applications.…”

Intracellular and Organic miRNA In Situ Detection

“…Some graphene-like fluorescence quenching analogs were reported for bioanalysis. Wu et al [22] presented a novel strategy by using PNA probes labeled with fluorophores; they were conjugated with nanometal-organic framework (NMOF) as a fluorescence quencher of the labeled PNA and developed for multiplexed miRNAs detection in living cancer cells. A multifunctional SnO 2 nanoprobe for target-cell-specific delivery and imaging with detection of intracellular miRNA was reported by Ju et al [23] (Fig.…”