Engineering enzyme-cleavable hybrid click capsules with a pH-sheddable coating for intracellular degradation

The ability for nano-engineered carriers to intelligently respond to biological variations is fundamental for their application as effective therapeutic delivery systems. Extensive research has been performed on carriers that respond to intracellular triggers such as pH gradients or changes in redox potential. However, the use of redox potential has limitations in such delivery systems, as the concentration and activity of reducing agents can be depleted in the endosomes or lysosomes upon usage. In contrast, the catalytic properties of enzymes allow for continuous regeneration and hence retention of high concentrations and activities of the enzymes within such compartments. Although the outer coating was not cross-linked, it was found to be stably attached to the cross-linked inner layers. This is likely to be due to the non-covalent hydrophobic interactions between the outer coating, peptide linker, and inner layers at physiological pH.