Detection of Pancreatic Cancer miRNA with Biocompatible Nitrogen-Doped Graphene Quantum Dots

Abstract

Early-stage pancreatic cancer remains challenging to detect, leading to a poor five-year patient survival rate. This obstacle necessitates the development of early detection approaches based on novel technologies and materials. In this work, the presence of a specific pancreatic cancer-derived miRNA (pre-miR-132) is detected using the fluorescence properties of biocompatible nitrogen-doped graphene quantum dots (NGQDs) synthesized using a bottom-up approach from a single glucosamine precursor. The sensor platform is comprised of slightly positively charged (1.14 ± 0.36 mV) NGQDs bound via π−π stacking and/or electrostatic interactions to the negatively charged (−22.4 ± 6.00 mV) bait ssDNA; together, they form a complex with a 20 nm average size. The NGQDs’ fluorescence distinguishes specific single-stranded DNA sequences due to bait–target complementarity, discriminating them from random control sequences with sensitivity in the micromolar range. Furthermore, this targetability can also detect the stem and loop portions of pre-miR-132, adding to the practicality of the biosensor. This non-invasive approach allows cancer-specific miRNA detection to facilitate early diagnosis of various forms of cancer.

Dual-Mode Fluorescence/Ultrasound Imaging with Biocompatible Metal-Doped Graphene Quantum Dots

“…43,44 Other sensing capabilities of these nanomaterials include miRNA and ssDNA detection, which could be utilized for cancer diagnosis. 45,46 Finally, our previous studies warrant that NGQDs can be utilized not only as imaging agents but also as successful drug delivery vehicles. For instance, the covalent attachment of ferrocene to NGQDs facilitates its enhanced delivery inside the cells and improves its redox-based cancer therapeutic effect in HeLa cells.…”

“…They possess a substantial surface area for functionalization, where ligands can be attached non-covalently to a graphene platform or covalently to a variety of oxygen-containing functional groups . These groups are protonated/deprotonated depending on the pH of the biological environment, causing a change in NGQDs’ fluorescence, which is utilized in biosensing of lower pH cancerous environments. , Other sensing capabilities of these nanomaterials include miRNA and ssDNA detection, which could be utilized for cancer diagnosis. , Finally, our previous studies warrant that NGQDs can be utilized not only as imaging agents but also as successful drug delivery vehicles. For instance, the covalent attachment of ferrocene to NGQDs facilitates its enhanced delivery inside the cells and improves its redox-based cancer therapeutic effect in HeLa cells …”

Formation of miRNA Nanoprobes—Conjugation Approaches Leading to the Functionalization

“…Ajgaonkar et al used graphene quantum dots doped with nitrogen as a slightly positively charged nanoplatform, non-covalently bonding the single-stranded DNA capture probe. The electrostatic binding of the capture probe and the π−π stacking onto the surface of the graphene-QDs altered their intrinsic fluorescence [ 76 ].…”

Low-dimensionality carbon-based biosensors: the new era of emerging technologies in bioanalytical chemistry

“…The GQD-based miRNA enzymatic biosensor platform was used to analyze human serum samples and achieved the detection of the analyte in the fM to pM range. The detection of miRNA was recently explored, designing a biosensing platform for the quantification of a specific pancreatic cancer–derived miRNA, expressed as pre-miR-132, based on the fluorescence variation of N-doped GQDs when bound to a bait ss-DNA sequence or the bait-target assemble, in a likely charge-transfer event [ 53 ]. The minimal concentration in the micromolar range indicates that these important biomarker sensors possess the potential for achieving ultrasensitive detection.…”