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

Autor: Rangrang Fan, Linrui Cai, Hao Liu, Hongxu Chen, Caili Chen, Gang Guo, Jianguo Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Pharmaceutical Analysis, Vol 14, Iss 3, Pp 321-334 (2024)
Druh dokumentu: article
ISSN: 2095-1779
DOI: 10.1016/j.jpha.2023.09.015
Popis: 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.
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