Thiol‐Disulfide Exchange Reaction Promoted Highly Efficient Cellular Uptake of Pyridyl Disulfide Appended Nonionic Polymers
Raju Bej, Arijit Ghosh, Jayita Sarkar, Benu Brata Das, Suhrit Ghosh
Abstract
The intracellular transport of molecules, macromolecules or materials is a key step in probing cellular structure and function, as well as regulating a plethora of physical and chemical events for treating disease. This communication reveals direct cellular uptake of pyridyl-disulfide (Py-Ds)-conjugated nonionic and biocompatible macromolecules with the aid of rapid exchange of the highly reactive Py-Ds groups with exofacial cell-surface thiols. Confocal microscopy and flow cytometry analysis confirmed highly efficient cellular uptake of Py-Ds-appended polymers (>50 % in 15 min) by avoiding lysosome as a consequence of thiol-disulfide exchange in the cell surface. In contrast, a control polymer lacking the Py-Ds group followed caveolae-mediated endocytosis. Other control polymers containing either the pyridine group (but not disulfide) or the disulfide group (but not pyridine) revealed significantly low cellular uptake, and thus essential role of the highly reactive Py-Ds group was established beyond doubt.