Combination drug therapy has become an effective clinical practice for cancer treatment because of low cytotoxicity by the synergistic effect of each medicine. Luminescent Au nanoclusters (Au NCs) were formulated into spherical polyethylene glycol (PEG)–Au NC-encapsulated drug–sodium butyrate (NaB) composite nanoparticles (PEG–Au NC–NaB-NPs) in the presence of PEG and NaB. Their effect on cancer cells was investigated using bio imaging, unravelling the mechanism of the endocytosis pathway and combination therapeutic interventions with a plant-based antimalarial drug artesunate (ART). PEG–Au NC–NaB-NPs showed bright red luminescence in the lysosomal compartment of the cells upon uptake predominantly through a caveolae-mediated pathway. Combination of PEG–Au NC–NaB-NPs with ART displayed enhanced therapeutic activity at a reduced dose compared to its individual doses and revealed heightened synergistic activity as identified from the combination index. The mechanism of synergism revealed elevated generation of reactive oxygen species with both NaB and ART, which disrupts mitochondrial membrane potential as evident from JC-1 staining. Remarkably, the histone deacetylase (HDAC) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay enlightened the role of NaB and ART in HDAC inhibition and DNA fragmentation, respectively. Thus, induction of apoptosis with the synergistic effect of both NaB and ART with its meticulous mechanism makes it a promising tool for combinational cancer therapy. In vivo activity of the NPs was evaluated on Daltons lymphoma ascites bearing mice, which exhibited significant reduction of tumor volume and viable tumor cells with a prolonged life span.

中文翻译：

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聚乙二醇包封的组蛋白脱乙酰酶抑制剂药物复合纳米粒与青蒿琥酯联合治疗

联合药物治疗已成为癌症治疗的有效临床实践，因为每种药物的协同作用具有较低的细胞毒性。在 PEG 和 NaB 存在的情况下，将发光金纳米簇 (Au NC) 配制成球形聚乙二醇 (PEG)-Au NC 封装的药物 - 丁酸钠 (NaB) 复合纳米粒子 (PEG-Au NC-NaB-NPs)。利用生物成像研究了它们对癌细胞的影响，揭示了胞吞途径的机制以及与植物抗疟药物青蒿琥酯（ART）的联合治疗干预。PEG-Au NC-NaB-NPs 主要通过小凹介导的途径被摄取后，在细胞的溶酶体区室中显示出亮红色发光。与单独剂量相比，PEG-Au NC-NaB-NPs 与 ART 的组合在减少的剂量下显示出增强的治疗活性，并且从组合指数中发现，显示出增强的协同活性。协同作用机制揭示了 NaB 和 ART 都会增加活性氧的产生，这从 JC-1 染色中可以明显看出，这会破坏线粒体膜电位。值得注意的是，组蛋白脱乙酰酶 (HDAC) 测定和末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定分别阐明了 NaB 和 ART 在 HDAC 抑制和 DNA 片段化中的作用。因此，NaB 和 ART 的协同作用诱导细胞凋亡及其细致的机制使其成为癌症联合治疗的有前途的工具。在患有道尔顿淋巴瘤腹水的小鼠上评估了纳米粒子的体内活性，这些小鼠表现出肿瘤体积显着减小，并且存活的肿瘤细胞具有延长的寿命。