Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis

An Hu; Jian-Wei Zhang; Li-Yun Yang; Pei-Pei Qiao; Dan Lu; Ya-Feng Yu

doi:10.3389/fbioe.2023.1183197

Curcumin-loaded graphene oxide quantum dots enhance otoprotective effects via blocking cuproptosis

Front Bioeng Biotechnol. 2023 Apr 19:11:1183197. doi: 10.3389/fbioe.2023.1183197. eCollection 2023.

Authors

An Hu^{1

2}, Jian-Wei Zhang³, Li-Yun Yang², Pei-Pei Qiao², Dan Lu², Ya-Feng Yu¹

Affiliations

¹ Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Otolaryngology-Head and Neck Surgery, Gongli Hospital, Second Military Medical University, Shanghai, China.
³ Department of Otolaryngology-Head and Neck Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

Abstract

Background: Cisplatin (CIS) is widely used to treat various cancers but can cause ototoxicity and sensory hair cell loss in the inner ear. Copper induces an excessive production of reactive oxygen species (ROS) in hair cells, leading to the development of various antioxidants. Methods and results: This study aimed to evaluate the potential antioxidant properties of curcumin (CUR) in the inner ear organ of corti-1 cells (OC1) and animal models (zebrafish and guinea pigs). Graphene oxide quantum dots (GOQDs) enabled CUR to penetrate the round window membrane (RWM) and maintain the concentration in the perilymph after inner ear administration. The results showed that CUR/GOQDs had favorable biocompatibility and strongly affected ROS generation induced by CIS in OC1 cells. DCFHDA Green staining demonstrated that CUR/GOQDs successfully reversed the decrease in mitochondrial membrane potential induced by CIS in vitro and rescued cells from early cuproptosis, which was confirmed by FDX1 staining. Additionally, the experiment found that CUR decreased the expression of cuproptosis proteins (FDX1, LIAS, and LIPT1) and increased the expression of the Bcl-2 protein. Conclusion: The results demonstrate that CUR/GOQDs is a promising therapeutic agent that can prevent CIS-induced ototoxicity by blocking the cuproptosis signal pathway.

Keywords: cuproptosis; curcumin; graphene oxide quantum dots; ototoxicity; reactive oxygen species.

Grants and funding

This study was funded by grants from Science and Technology the Bureau of Suzhou (No. SLT202007); Clinical Medical Center of Suzhou (No. SZLCYXZX202102); The National Natural Science Foundation of China (No. 82271162); The Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University (No. GZK 1202209); The Pudong New Area health system discipline leader project (No. PWRd 2021-04); Shanghai Pudong Science and Technology Development Foundation (No. PKJ2021‐Y13); Medical discipline construction project of health system in Pudong New Area (No. PWYts 2021-15 and No. 2022GPY-A05); Key sub specialty construction project of Pudong Health Bureau of Shanghai (No. PWZy 2020-06); Research Grant for Health Science and Technology of Pudong Health Bureau of Shanghai (No. PW2019D-4) and Key Specialist Construction Project of Health Bureau of Shanghai (No. ZK 2019C06).