(260bc) Locked Nucleic Acid-Wrapped Single-Walled Carbon Nanotubes Based Optical Sensor for microRNAs Detection

As master regulators of cellular processes, microRNAs have assumed a flagship role in disease diagnosis and treatment, acting both as biomarkers and therapeutic targets for a range of diseases, including early-stage cancer prognosis.^1-2 Single-walled carbon nanotubes (SWCNTs) offer advantageous fluorescence properties for optically detecting microRNA that would enable an in vivo and nearly ideal high-throughput approach to profiling gene expression. Benefiting from indefinite photostability, sensitivities to single-nucleotide polymorphisms, and optical transparency to biological tissue,³ we developed an optical microRNA sensor based on SWCNT fluorescence. Through non-covalent SWCNT surface functionalization, this sensor interfaces locked nucleic acids (LNAs) with SWCNTs to detect microRNA-21, a key target for the prognosis of several different types of cancers. This sensor exhibited an unprecedented SWCNT fluorescence sensitivity towards RNA, achieving sub-micromolar sensitivities within a 5-minute sensor response time. The SWCNT fluorescence response was shown to vary with microRNA-21 concentration, and it was shown to be both sequence- and oligonucleotide dependent when screened in vitro against alternative microRNA and analogous DNA probes. In the presence of microRNA-21, the LNA-wrapped SWCNTs undergo a chiral-specific fluorescence increase and wavelength shift, with an initial effective binding rate constant of 2.3 x 103 a.u. μM-1 s-1 for the (9,5) SWCNT. Low-energy electron holography images show that LNA assumes a helical conformation on the SWCNT surface similar to the chiral-specific conformation observed for DNA-wrapped SWCNTs, suggesting an analogous hybridization and sensing mechanism. The chirality-dependent molecular fingerprinting of microRNA shown in this study provides a promising platform for multimodal microRNA profiling.

References

 

(1) T.A. Farazi, J.I. Spitzer, P. Morozov, T. Tuschl, J. Pathol., 2011, 223 (2),102.

(2) E.A. Hunt, D. Broyles, T. Head, S.K. Deo, Annu Rev Anal Chem, 2015, 8, 217.

(3) Boghossian, A. A.; Zhang, J.; Barone, P. W.; Reuel, N. F.; Kim, J.-H.; Heller, D. A.; Ahn, J.-H.; Hilmer, A. J.; Rwei, A.; Arkalgud, J. R.; Zhang, C. T.; Strano, M. S. ChemSusChem 2011, 4 (7), 848.