Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Rangrang Fan; Linrui Cai; Hao Liu; Hongxu Chen; Caili Chen; Gang Guo; Jianguo Xu

doi:10.1016/j.jpha.2023.09.015

Volume 14 Issue 3

Mar. 2024

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Rangrang Fan, Linrui Cai, Hao Liu, Hongxu Chen, Caili Chen, Gang Guo, Jianguo Xu. Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 321-334. doi: 10.1016/j.jpha.2023.09.015

Citation:

Rangrang Fan, Linrui Cai, Hao Liu, Hongxu Chen, Caili Chen, Gang Guo, Jianguo Xu. Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 321-334. doi: 10.1016/j.jpha.2023.09.015

Citation:

Rangrang Fan, Linrui Cai, Hao Liu, Hongxu Chen, Caili Chen, Gang Guo, Jianguo Xu. Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 321-334. doi: 10.1016/j.jpha.2023.09.015

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Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

doi: 10.1016/j.jpha.2023.09.015

a. Department of Neurosurgery and Institute of Neurosurgery, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China;
b. NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, National Drug Clinical-Trial Institution, West China Second Hospital, Sichuan University, Chengdu, 610041, China;
c. Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, 453000, China

Funds:

This study was supported by the National Natural Science Foundation of China (Grant Nos.: 82102767 and 82002655), the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University, China (Grant No.: 2020HXFH036), the Knowledge Innovation Program of the Chinese Academy of Sciences, China (Grant No.: JH2022007), the Cultivation Project of Basic Medical College of Xinxiang Medical University, China (Grant No.: JCYXYKY202112), and the Key Project of Science and Technology of Henan Province, China (Grant No.: 222102310260).

Received Date: Jun. 16, 2023
Accepted Date: Sep. 19, 2023
Rev Recd Date: Sep. 18, 2023
Publish Date: Sep. 23, 2023

Abstract

Abstract

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met–GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe³⁺) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
- Metformin,
- Glucose oxidase,
- Metabolism disruption,
- Tumor starvation,
- Combination cancer therapy

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References(64)

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