Research Projects

Understanding cellular organelle function, disease progression, morphology, dynamics, and inter-organelle cross-talk is crucial for developing live-cell penetrating organelle-targeted multifunctional probes. Rotaxanes, mechanically interlocked molecules, have been used in molecular machines, but they are less explored in the complex environment of live cells. Rotaxane absorbs NIR-II region (1000-1700 nm) light, exhibiting spatio-temporal resolution compared to NIR-I probes. However, organic NIR-II dyes are still in the developmental phase, and biological research is hindered by the inaccessibility of suitable functional probes. Original organic NIR-II probes are limited in their cellular imaging due to photobleaching, poor water solubility, tendency to aggregate, and inadequate stability in live cells. The "cyanine limit" is a key molecular design obstacle for constructing NIR-II Cy probes for imaging diagnostics. A proposed solution is to entrap a NIR-II dye within a sterically shielded macrocycle to build rotaxane stabilized by mechanical bond. Multifunctional NIR-II rotaxanes could open new avenues for real-time tracking and monitoring of organelle dynamics and inter-organelle cross-talk. The development of water-soluble ultrabright with huge Stokes shift NIR-II fluorescent PEGylated rotaxanes in conjugation with targeted MRI contrast agents could be the next milestone on the roadmap for rotaxane molecules for biomedical applications. Designing NIR-II rotaxanes to target overexpressed receptors and enzymes at the tumor site, organelle activatable ratiometric NIR-II rotaxanes for quantification of analytes, and bioconjugation of de novo designed peptides with multifunctional rotaxanes could lead to targeted image-guided manipulation of cellular function and fate.