Positively or negatively charged defect-free graphene can increase the delivery of enzymes to fibroblasts derived from patients with mucopolysaccharidosis 6 and Pompe disease, according to a new study published in Nanoscale.
These findings suggest that graphene-based materials could potentially be used as carriers of enzyme replacement therapy (ERT).
ERT is known to result in significant clinical improvements in diseases like Pompe disease. However, there are challenges associated with the delivery of the replacement enzyme to the cells and tissues in the body.
Read more about ERT and other therapies for Pompe disease
In the present study, a team of researchers led by Sandra Vranic, PhD, from the University of Manchester in the United Kingdom explored the potential use of graphene-based materials, which represent a promising platform for the delivery of ERT due to their dimensionality and interaction with cells, to deliver lysosomal enzymes to fibroblasts.
The team used fibroblasts from patients with mucopolysaccharidosis 6, also called Maroteaux-Lamy syndrome, and Pompe disease, as well as defect-free graphene with positive or negative surface charge and graphene oxide with different dimensions.
They showed that all graphene-based materials had excellent biocompatibility up to a concentration of 100 μg/mL. However, there was a “noticeable difference in the uptake profile of the materials.” While none of the graphene oxide was taken up by cells, graphene with positive or negative surface charge was taken up efficiently and localized to the lysosomes.
The researchers also demonstrated that cationic graphene flakes could be used to carry arylsulfatase B, the enzyme that is missing in Maroteaux-Lamy syndrome, to the cells. The enzyme retained its activity and exerted a better biological effect when it was delivered this way than when it was delivered on its own.
“This study lays the groundwork for the potential use of graphene-based materials as carriers for enzyme replacement therapy in lysosomal storage disorders,” the researchers concluded.
Chen Y, Taufiq T, Zeng N, et al. Defect-free graphene enhances enzyme delivery to fibroblasts derived from patients with lysosomal storage disorders. Nanoscale. Published online May 11, 2023. doi:10.1039/d2nr04971f