Study Probes the Chemical Basis of Cell-Penetrating Poly(disulfide) Uptake
- Poly(disulfide)s are dynamic-covalent polymers whose guanidinium-rich chains cross cell membranes via thiol-mediated uptake, engaging surface thiols rather than classical endocytosis.
- This study probes the chemical basis of that uptake, linking polymer structure and disulfide exchange to membrane translocation and cytosolic release.
- It reinforces poly(disulfide)s as a macromolecular delivery modality for proteins, antibodies, and nucleic acids, bypassing lysosomal degradation.
💡 Points
Skipping endocytosis entirely is the real prize: LNPs and most CPPs still have to escape an endosome, and that's where most of your payload dies. A dynamic-covalent scaffold means guanidinium density and disulfide exchange rate are dial-in knobs, not a peptide sequence you're stuck re-screening. Worth revisiting for antibody or siRNA payloads where endosomal escape is currently the bottleneck.