PEGylated Graphene Oxide as a Nanocarrier Assists Alpha Lipoic Acid Mitigating Hypoxia Induced Mitochondrial Dysfunction

Due to its hydrophilicity and biocompatibility, PEGylated graphene oxide (GO-PEG) has been reported as a potential nanocarrier for anticancer therapeutic agents. Alpha lipoic acid (α-LA), a cofactor in multienzyme complexes, plays a central role in mitochondrial energy metabolism. In this study, we first observed that GO-PEG could rapidly enter rat cardiomyocyte H9C2 cells and colocalize with mitochondria by confocal laser microscopy using Rhodamine B (RhB) as a probe. Next, α-LA was loaded onto GO-PEG-RhB through π-π stacking and hydrophobic interactions, forming a GO-PEG-RhB/α-LA complex with a 21.4% loading rate and 42.8% encapsulation efficiency. <i>In vitro</i> assays showed that GO-PEG-RhB/α-LA significantly mitigated mitochondrial dysfunction compared with free α-LA in a hypoxia-induced H9C2 cell model treated with CoCl₂ via the regulation of mitochondrial dynamics and biogenesis signaling pathways. GO-PEG-RhB/α-LA clearly showed better mitochondrial targeting and α-LA release in mitochondria than free α-LA. After oral administration in a hypoxia-induced mouse model, GO-PEG-RhB/α-LA again showed a better recovery effect on hypoxia-induced mitochondrial dysfunction than free α-LA. Taken together, our data demonstrate the feasibility of GO-PEG as a nanocarrier for mitochondrial-targeted drugs. This work broadens the application of graphene-based nanocarriers in biomedical fields.