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静脉注射用二甲双胍-Cu(II)-表没食子儿茶素没食子酸酯配位聚合物纳米粒子用于电热增强的双药协同肿瘤治疗。

Intravenous injectable metformin-Cu(II)-EGCG coordination polymer nanoparticles for electrothermally enhanced dual-drug synergistic tumor therapy.

机构信息

Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. China.

出版信息

J Mater Chem B. 2024 Aug 14;12(32):7934-7945. doi: 10.1039/d4tb01017e.

DOI:10.1039/d4tb01017e
PMID:39037293
Abstract

Intravenous injectable metformin-Cu(II)-EGCG infinite coordination polymer nanoparticles (metformin-Cu(II)-EGCG ICP NPs) have been synthesized, and an efficient strategy for synergistic tumor therapy by utilizing these nanoparticles in conjunction with micro-electrothermal needles (MENs) was proposed. These nanoparticles display exceptional uniformity with a diameter of 117.5 ± 53.3 nm, exhibit an extraordinary drug loading capacity of 90% and allow for precise control over the drug ratio within the range of 1 : 1 to 1 : 20 while maintaining excellent thermal stability. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction were employed to determine their chemical structure and coordination state. The combination index (CI) value of the metformin-Cu(II)-EGCG ICP NPs was calculated to be 0.19, surpassing that of the two individual drugs and metformin mixed with EGCG (0.98). Importantly, upon intravenous injection, metformin in nanoparticles demonstrated exceptional stability in the bloodstream, while both drugs were rapidly released within the acidic tumor microenvironment. Animal experiments showcased an impressive tumor inhibition rate of 100% within a mere 20-day time frame after the synergistic therapy with a lower dosage (5.0 mg kg of nanoparticles), coupled with a minimal tumor recurrence rate of only 18.75% over a 60-day observation period. These findings indicate the promising prospects of these nanoparticles in tumor treatment.

摘要

静脉注射用二甲双胍-Cu(II)-表没食子儿茶素没食子酸酯无限配位聚合物纳米粒子(metformin-Cu(II)-EGCG ICP NPs)已被合成,并提出了一种利用这些纳米粒子与微电热针(MENs)联合进行协同肿瘤治疗的有效策略。这些纳米粒子具有异常的均匀性,直径为 117.5±53.3nm,表现出非凡的载药能力(高达 90%),并能在 1:1 至 1:20 的范围内精确控制药物比例,同时保持出色的热稳定性。傅里叶变换红外光谱、X 射线光电子能谱和 X 射线衍射用于确定其化学结构和配位状态。二甲双胍-Cu(II)-EGCG ICP NPs 的组合指数(CI)值计算为 0.19,超过了两种单独药物和二甲双胍与 EGCG 混合(0.98)的 CI 值。重要的是,静脉注射后,纳米粒子中的二甲双胍在血液中表现出异常的稳定性,而两种药物在酸性肿瘤微环境中迅速释放。动物实验表明,在协同治疗(5.0mg kg 纳米粒子)的低剂量下,仅 20 天内的肿瘤抑制率达到 100%,60 天观察期内的肿瘤复发率仅为 18.75%。这些发现表明这些纳米粒子在肿瘤治疗方面具有广阔的应用前景。

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