A Functional Carbon Dots Induce Ferroptosis By Suppressing PLPP4 Activity to Inhibit Glioblastoma Growth

45 Pages Posted: 24 Apr 2023

See all articles by Kun Deng

Kun Deng

Central South University

Lianglin Zhang

Central South University

Wei Gao

Central South University

Xiang Lin

Central South University

Xinmiao Long

Central South University

Yang Wang

Central South University - Department of of Integrated Traditional & Western Medicine

Minghua Wu

Central South University - Cancer Research Institute; Central South University - Department of of Integrated Traditional & Western Medicine; Government of the People's Republic of China - Key Laboratory of Carcinogenesis

Abstract

Glioblastoma is a fatal primary brain cancer lacking effective therapeutic drugs. The presence of the blood-brain barrier (BBB) severely hinders the delivery of drugs to the brain. In recent years, nanoparticles, especially carbon dots (CDs), are promising drug delivery strategy for CNS diseases. Here, we synthesized a novel carbon dots(MGA-CDs)for glioblastoma treatment by hydrothermal method using metformin and gallic acid as precursor. MGA-CDs shows dominant BBB permeability and sensitive anti-tumor activity. In addition, MGA-CDs exhibits significant capability of targeting tumor cells mitochondria without the aid of anyextra targeting molecules, resulting in the shrunken of mitochondria and reduced numbers of mitochondrial cristae. Transcriptome profiling suggested that MGA-CDs disturbs the glycerophospholipid metabolism pathway by inhibiting the expression of PLPP4,thereby inducing ferroptosis. The efficient therapeutic potency of MGA-CDs is further confirmed in human-derived orthotopic glioblastoma mice model. MGA-CDs significantly inhibited the growth of intracranial tumors and prolonged the survival of tumor-bearing mice. This work presents a viable strategy that development of CDs-based novel therapeutic agent for glioblastoma.

Note:
Funding Information: This work was supported by the National Natural Science Foundation of China (82073096, 82274371), the Fundamental Research Funds for the Central Universities of Central South University (CX20220324).

Conflict of Interests: The authors declare no competing financial interests.

Ethical Approval: All animal experiments were approved by the Animal Care and Use Committee of Central South University.

Keywords: Glioblastoma, Carbon dots, mitochondria, glycerophospholipid metabolism, PLPP4, Ferroptosis

Suggested Citation

Deng, Kun and Zhang, Lianglin and Gao, Wei and Lin, Xiang and Long, Xinmiao and Wang, Yang and Wu, Minghua, A Functional Carbon Dots Induce Ferroptosis By Suppressing PLPP4 Activity to Inhibit Glioblastoma Growth. Available at SSRN: https://ssrn.com/abstract=4423142 or http://dx.doi.org/10.2139/ssrn.4423142

Kun Deng

Central South University ( email )

Changsha, 410083
China

Lianglin Zhang

Central South University ( email )

Changsha, 410083
China

Wei Gao

Central South University ( email )

Changsha, 410083
China

Xiang Lin

Central South University ( email )

Changsha, 410083
China

Xinmiao Long

Central South University ( email )

Changsha, 410083
China

Yang Wang

Central South University - Department of of Integrated Traditional & Western Medicine ( email )

Minghua Wu (Contact Author)

Central South University - Cancer Research Institute ( email )

China

Central South University - Department of of Integrated Traditional & Western Medicine ( email )

Government of the People's Republic of China - Key Laboratory of Carcinogenesis ( email )

China

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