Thiol‐Disulfide Exchange Reaction Promoted Highly Efficient Cellular Uptake of Pyridyl Disulfide Appended Nonionic Polymers. (25th June 2020)

• Record Type: Journal Article
• Authors: Bej, Raju; Ghosh, Arijit; Sarkar, Jayita; Das, Benu Brata; Ghosh, Suhrit
• Is Part Of: Chembiochem. Volume 21:Number 20(2020)
• Page Start: 2921
• Page End: 2926
• Publication Date: 2020-06-25
• Subjects: bioconjugation -- cell-penetrating polymer -- cellular uptake -- pyridyl disulfide -- thiol-disulfide exchange; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000303
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : It takes two : Pyridyl‐disulfide (Py−Ds) conjugated non‐ionic nontoxic polymers exhibit cellular uptake by thiol‐disulfide exchange with exofacial cell‐surface thiols without going through the endocytosis pathway. Control experiments establish essential role of the Py−Ds group as neither pyridine‐ nor an aliphatic disulfide‐appended polymer shows similar cellular uptake.