A novel concurrent determination of dual blue–green luminescent carbon dots in single excitation wavelength: Highly reliable simultaneous targeting and imaging of CA125 and CA15-3 tumor markers and cells via bi-color FRET phenomenon based on CDs-MoS2 heterojunction

Simultaneous determination of several biological targets by fluorescence techniques with a single test mode is highly desirable for diseases diagnostics and early cancer recognitions [1, 2]. For the first time, a simultaneous designed fluorescence resonance energy transfer (FRET) strategy based on coupling two different carbon dots (CDs-NH2, CDs-COOH) conjugating antibodies was fabricated. The efficient two bio-CDs were synthesized separately having strong fluorescence maxima at 326 nm and 443 nm. The monodispersed MoS2 nanosheets were functionalized with ssDNA related aptamers and applied as quencher. Exclusive optical, surface state, chemical structure and electronic properties of the synthesized nanomaterials have been investigated. More importantly, the solution containing both of the CDs conjugating to CA125 as Ab1 and CA15-3 as Ab2 (CD1-Ab1, CD2-Ab2) could be excited by single wavelength excitation. Inspired by these facts, we fabricated a selective and sensitive fluorescence nanosensor for simultaneous targeting of tumor markers by simple mixing blue and green-emission fluorescent CDs. In the absence of CA125 and CA15-3 target antigens the fluorescence of the antibody labeled CD1 and CD2, quenched with MoS2 due to energy transfer (FRET) process, while with addition of target antigens, the formation of immunocomplex between CDs-Ab probe, antigen, and ssDNA leading to the release of MoS2, resulting in the distinct changes in fluorescence response. The response of the architectured nanoassembly enhanced gradually with the increase in concentration of targets in the range of 50 fg/mL to 8 pg/mL with the 5.0 fg/mL as calculated limit of detection for CA125, and the response was found to be linear with the concentration in the range of 1.0 to 35 pg/mL for CA15-3 and the calculated limit of detection was 0.5 pg/mL. Finally, CDs-antibody hybrids were used in selective tracking and imaging of the cancer cells over MCF-7 and OVCAR-3 cells lines. The obtained results implying the potential applications of presented assay for cancer diagnosis, the selectivity and sensitivity of this fluorescent nanosensor over other markers were carefully investigated.