Chiral Mechanism Of Intracellular Nanodimer And The Ultrasensitive Biosensors For Telomerase And Folic Acid

In this paper, self-assembly nanoparticle dimers were prepared using achiral building blocks. Based on these structures, the interaction between assembles and cell were studied. And a high sensitive and selective biosensor for intracellular telomerase detection was established through chiroptical activity. Moreover, the SERS based ultra-sensitive sensor for the food nutriment of folic acid was designed. Finally, a new hierarchical plasmonic nanorods dimer and upconversion core-satellite Nanoassembly was constructed for multimodal imaging-guided combination phototherapy.First, through precise DNA molecule self-assembly, different plasmonic metal-semiconductor heterodimer composed of Au, Ag and quantum dots(QDs) NPs in high yield were obtained, which had a distinct diverse chirality effect in plasmonic region. The semiconductor QDs dimers showed a weak circular dichroism(CD) signal, while enhanced signals were observed after coupling with Au or Ag. This interesting chiroptical effect, which originated from the assembled chiral geometry were proved by cyro-TEM.Secondly, the interaction between assembles and cell were studied by chiral Au NP dimers first time. It has been observed from CD signal that the chirality was reversed before and after the dimer get into cell. The chiral conformations of building blocks were changed under the different pH and the concentration of protein and glucose in and out of cell, which were proved by cyro-TEM. In addition, the intracellular dimer can yield more singlet oxygen under left circular polarized light(LCP) than right circular polarized light(RCP). While the dimer in solution the situation was opposite, due to the different chiral conformations, which holds great evidence for chirality reversal in cell.Thirdly, a DNA-driven Au heterodimer for ultra-sensitive intracellular telomerase detection was fabricated. The telomerase activity was specifically quantified using CD intensity in situ after internalization of the heterodimer into cancer cell, which have a high biocompatible and stability in living cells. Moreover, the results clearly illustrated that this method had a remarkable linear range from 0.8×10-12 IU to 32×10-12 IU, and the limit of detection(LOD) for telomerase activity was 1.7×10-15 IU in a single HeLa cell. This strategy paves the way for chirality-based ultrasensitive detection of intracellular cancer markers.Fourthly, using gold-silver nanoparticle(AuNP-AgNP) heterodimers assembled by folic acid(FA) antibody and antigen, an ultrasensitive surface-enhanced Raman scattering(SERS) biosensor for the detection of folic acid in food was developed. The limit of detection(LOD) was as low as 0.86 pg/m L, which was the lowest reported so far.Fifthly, a DNA-based hierarchical core-satellite nanostructure with plasmonic gold nanorod(NR) dimers and upconversion nanoparticles was generated. Using this novel theranostic agent, combined photothermal therapy and photodynamic therapy were carried out under the guidance of multimodal imaging techniques such as magnetic resonance imaging(MRI), upconversion luminesce(UCL), X-ray computed tomography(CT) and photoacoustics(PA), and the results demonstrated that the photothermal efficiency of nanostructures was two-fold than that of the single NR assembly. Furthermore, tumors treated with the NR dimer assemblies were completely eliminated in vivo, which expands the programmed nanoassemblies for clinical application.