title: Unlocking a caged lysosomal protein from a polymeric nanogel with a pH trigger.
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.
authors.affiliation: Department of Chemistry and ‡Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst , 710 N. Pleasant Street, Amherst, Massachusetts 01003, United States.
authors.forename: Mijanur Rahaman
authors.initials: MR
authors.lastname: Molla
authors.forename: Tyler
authors.initials: T
authors.lastname: Marcinko
authors.forename: Priyaa
authors.initials: P
authors.lastname: Prasad
authors.forename: Derrick
authors.initials: D
authors.lastname: Deming
authors.forename: Scott C
authors.initials: SC
authors.lastname: Garman
authors.forename: S
authors.initials: S
authors.lastname: Thayumanavan
mesh_terms: D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000080385:Nanogels; D011108:Polymers; D011506:Proteins; C018589:lysosomal proteins; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine