2. Academic Validation
  3. PEGylated Graphene Oxide as a Nanocarrier Assists Alpha Lipoic Acid Mitigating Hypoxia Induced Mitochondrial Dysfunction

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

  • ACS Appl Bio Mater. 2026 Feb 2;9(3):1352-1364. doi: 10.1021/acsabm.5c01802.
Liren Wu 1,  Bingjie Hao 2,  Zheyu Fan 1,  Qiaoqiao Zheng 1,  Boyi Song 1,  Xiao Feng 1,  Shaoliang Lin 3,  Xiaoyu Huang 2,  Ping Shi 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
  • 2 State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
  • 3 Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
PMID: 41535114 DOI: 10.1021/acsabm.5c01802
Abstract

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. In vitro 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.

Keywords

PEGylated graphene oxide; alpha lipoic acid; drug delivery; hypoxia; mitochondrial dysfunction.

Figures
Products