Fan Rangrang, Cai Linrui, Liu Hao, Chen Hongxu, Chen Caili, Guo Gang, Xu Jianguo
Department of Neurosurgery and Institute of Neurosurgery, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
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.
J Pharm Anal. 2024 Mar;14(3):321-334. doi: 10.1016/j.jpha.2023.09.015. Epub 2023 Sep 23.
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 . 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 (Fe) 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 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 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.
尽管经过了数十年的实验室和临床试验，但乳腺癌仍然是女性癌症相关疾病负担的主要原因。考虑到二甲双胍（Met）的代谢破坏作用以及葡萄糖氧化酶（GOx）诱导的癌细胞饥饿，在将它们有效递送至肿瘤部位后，GOx和Met可能会消耗大量葡萄糖并产生足够的过氧化氢。在此，构建了一种pH响应型表没食子儿茶素没食子酸酯（EGCG）共轭的低分子量壳聚糖（LC-EGCG，LE）纳米颗粒（Met-GOx/Fe@LE NPs）。该纳米平台中铁离子（Fe）与EGCG之间的配位作用可通过芬顿反应增强化学动力疗法的疗效。Met-GOx/Fe@LE NPs可使GOx保持其酶活性，同时提高其稳定性。此外，这种pH响应型纳米平台呈现出可控的药物释放行为。一项生物分布研究表明，由该纳米平台递送的GOx在颅内的蓄积量比游离药物高3.6倍。抗癌结果表明，这种代谢破坏/饥饿/化学动力三联组合疗法可诱导肿瘤细胞凋亡/死亡增加并降低其增殖。这种三联组合疗法对于高效靶向癌症治疗具有前景。
