Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy
10.1016/j.jpha.2023.09.015
- Author:
Fan RANGRANG
1
;
Cai LINRUI
;
Liu HAO
;
Chen HONGXU
;
Chen CAILI
;
Guo GANG
;
Xu JIANGUO
Author Information
1. Department of Neurosurgery and Institute of Neurosurgery,Cancer Center and State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu,610041,China
- Keywords:
Metformin;
Glucose oxidase;
Metabolism disruption;
Tumor starvation;
Combination cancer therapy
- From:
Journal of Pharmaceutical Analysis
2024;14(3):321-334
- CountryChina
- Language:Chinese
-
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 nano-platform 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.
