Enzyme replacement therapy shows remarkable clinical improvement in treating lysosomal storage disorders. However, this therapeutic approach is hampered by limitations in the delivery of the
enzyme to cells and tissues. Therefore, there is an urgent, unmet clinical need to develop new strategies to enhance the
enzyme delivery to diseased cells.
Graphene-based materials, due to their dimensionality and favourable pattern of interaction with cells, represent a promising platform for the loading and delivery of therapeutic cargo. Herein, the potential use of
graphene-based materials, including defect-free
graphene with positive or negative surface charge and
graphene oxide with different lateral dimensions, was investigated for the delivery of lysosomal
enzymes in fibroblasts derived from patients with
Mucopolysaccharidosis VI and
Pompe disease. We report excellent biocompatibility of all
graphene-based materials up to a concentration of 100 μg mL-1 in the cell lines studied. In addition, a noticeable difference in the uptake profile of the materials was observed. Neither type of
graphene oxide was taken up by the cells to a significant extent. In contrast, the two types of
graphene were efficiently taken up, localizing in the lysosomes. Furthermore, we demonstrate that cationic
graphene flakes can be used as carriers for
arylsulfatase B enzyme, for the delivery of the lacking
enzyme to the lysosomes of
Mucopolysaccharidosis VI fibroblasts.
Arylsulfatase B complexed with cationic
graphene flakes not only retained the enzymatic activity, but also exerted
biological effects almost twice as high as
arylsulfatase B alone in the clearance of the substrate in
Mucopolysaccharidosis VI fibroblasts. This study lays the groundwork for the potential use of
graphene-based materials as carriers for
enzyme replacement therapy in lysosomal storage disorders.