Unlocking a Caged Lysosomal Protein from a Polymeric
Nanogel with a pH Trigger
- Publication date
- Publisher
Abstract
A polymeric nanogel
has been used to sequester and turn off a lysosomal
protein, acid α-glucosidase (GAA). The nanogel contains a β-thiopropionate
cross-linker, which endows the nanogel with pH-sensitivity. While
encapsulation of the enzyme fully turns off its activity, approximately
75% of the activity is recovered upon reducing the pH to 5.0. The
recovered activity is ascribed to pH-induced degradation of the β-thiopropionate
cross-linker causing the swelling of the nanogel and ultimately causing
the release of the enzyme. We envision that strategies for sequestering
protein molecules and releasing them at lysosomal pH might open up
new directions for therapeutic treatment of lysosomal storage diseases