Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects./nMethods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis./nResults: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK)./nConclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

中文翻译：

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果糖包被的埃斯特罗姆银可通过抑制PDK来改变葡萄糖代谢，从而促进ROS依赖的凋亡，从而抑制骨肉瘤的生长和转移。

骨肉瘤是一种易于转移的常见恶性骨癌。仍然需要更安全，更有效的策略来抑制骨肉瘤的生长和肺转移。我们最近提出了一种纯物理方法来制造埃斯特罗姆级的银颗粒（AgÅPs），并确定了果糖涂层的AgÅPs（F-AgÅPs）对肺癌和胰腺癌的抗肿瘤功效。我们的研究利用一种优化的方法来获得较小的F-AgÅP，旨在评估F-AgÅP是否可以用作骨肉瘤治疗的有效和安全剂。我们还调查了细胞凋亡通过改变感应是否葡萄糖代谢表型有助于F-AgÅPs诱导抗骨肉瘤effects./n方法：开发了一种改进的方法来制备较小的F-AgÅP。将F-AgÅPs的抗肿瘤，抗转移和促生存作用及其对健康组织的毒性与皮下或原位荷骨肉瘤的裸鼠中的顺铂（骨肉瘤治疗的一线化疗药物）进行了比较。通过测试小鼠血清，组织，尿液和粪便中银的含量来评估F-AgÅPs的药代动力学，生物分布和排泄。进行了一系列体外测定，以评估凋亡的诱导是否介导F-AgÅP对骨肉瘤细胞的杀伤作用，以及葡萄糖代谢表型的改变是否有助于F-AgÅPs诱导的凋亡。新获得的F-AgÅPs（9.38±4.11 nm）在不同的生物介质或水溶液中具有良好的稳定性，并且比顺铂在抑制荷瘤肉瘤裸鼠静脉注射后的肿瘤生长，改善存活率，减轻骨溶解和预防肺转移方面比顺铂更有效。注射，但在正常组织中耐受良好。注射后一周，约有68％的F-AgÅP通过粪便排出体外。F-AgÅPs诱导的活性氧（ROS） -依赖性骨肉瘤细胞的细胞凋亡而不是正常细胞，通过抑制丙酮酸脱氢酶激酶（PDK）由于它们的能力从糖酵解线粒体氧化骨肉瘤细胞的选择性移葡萄糖代谢./Ñ结论： 我们的研究表明F-AgÅP作为骨肉瘤治疗的强大选择性抗癌药的前景广阔。