Although nanotechnology has been rapidly developed and applied in tumor targeting, the outcome of chemotherapy remains greatly restricted by the toxicity of cytotoxic drugs in normal tissues and cells. Therefore, the development of alternative delivery systems, with few side effects in normal cells, has attracted increasing attention. Energy restriction is a novel and promising approach to cancer treatment, which can restrict tumor growth via inhibition of cellular energy metabolism. In this study, a novel tumor targeting system, based on folate-conjugated bovine serum albumin (BSA), was developed to co-deliver albendazole and nanosilver simultaneously, to restrain the energy metabolism of tumor cells. This nanosystem showed stronger anti-tumor efficacy than those using nanoparticles without folic acid modification, nanosilver, or albendazole, both in vitro and in vivo. This nanosystem depleted cellular ATP via direct inhibition of glycolytic enzymes and mitochondrial damage, resulting in inhibition of proliferation, cell-cycle arrest, and apoptosis of tumor cells. The enhanced anti-tumor activity contributed to the tumor-targeting ability of this system, resulting in specific energy inhibition in tumor cells. Toxicity evaluation was performed to confirm the safety of this system. This nanosystem provides an efficient and safe strategy for tumor therapy.

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尽管纳米技术已经迅速发展并应用于肿瘤靶向，但是化学疗法的结果仍然受到正常组织和细胞中细胞毒性药物毒性的极大限制。因此，在正常细胞中几乎没有副作用的替代递送系统的开发引起了越来越多的关注。能量限制是一种新颖且有前途的癌症治疗方法，可通过抑制细胞能量代谢来限制肿瘤的生长。在这项研究中，开发了一种基于叶酸偶联牛血清白蛋白（BSA）的新型肿瘤靶向系统，以同时共同递送阿苯达唑和纳米银，从而抑制肿瘤细胞的能量代谢。与使用未经叶酸修饰，纳米银或阿苯达唑的纳米颗粒相比，这种纳米系统显示出更强的抗肿瘤功效，体外和体内。这种纳米系统通过直接抑制糖酵解酶和线粒体破坏而耗尽了细胞ATP，从而抑制了肿瘤细胞的增殖，细胞周期停滞和凋亡。增强的抗肿瘤活性有助于该系统的肿瘤靶向能力，从而导致肿瘤细胞中的特定能量抑制。进行毒性评估以确认该系统的安全性。该纳米系统为肿瘤治疗提供了有效而安全的策略。

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