The conventional chemotherapeutic agents used in the treatment of human malignancies are directed nonspecifically against both malignant and nonmalignant cells, often limiting their efficacy with having serious side effects. Recent development of drug delivery vehicles has opened up the possibility of targeted drug delivery systems with the potential of achieving maximum efficacy with minimal toxicity. The possibility of using a nanomaterial as a combinational drug component is intuitively evident as it would compensate the toxicity level by enhancing drug delivery efficiency. Additionally, cell-specific cytotoxicity (reported earlier by our group) of the nanovehicle itself may potentiate a more effective targeted cell killing. In this paper, we explore the possibility of using gold nanoparticles playing the dual role of an anticancer agent and a carrier of a chemotherapeutic drug. This is demonstrated using vincristine sulfate (VS), salt of an alkaloid often used in the treatment of multiple myeloma (MM), and U266 as a test MM cell line. The drug VS shows the expected G2-M-phase arrest of cells. Notably, bare gold nanoparticle shows arrest of the S phase cells that may be particularly important in case of slow-growing malignancies like MM where most of the cells remain in G1 phase of the cell cycle. The VS conjugated gold retains the activity of both gold nanoparticle and VS leading to a synergistic rise of the apoptotic cell population.

中文翻译：

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纳米颗粒作为药物载体和药物的双重作用。

用于治疗人类恶性肿瘤的常规化学治疗剂非特异性地针对恶性和非恶性细胞，常常限制其功效并具有严重的副作用。药物输送工具的最新发展开辟了靶向药物输送系统的可能性，该系统具有在最小的毒性下实现最大功效的潜力。使用纳米材料作为组合药物成分的可能性在直观上是显而易见的，因为它将通过提高药物输送效率来补偿毒性水平。另外，纳米载体本身的细胞特异性细胞毒性（我们小组较早前报道）可能会增强靶向细胞的杀伤效果。在本文中，我们探索了使用金纳米颗粒同时发挥抗癌剂和化疗药物载体双重作用的可能性。使用硫酸长春新碱（VS），常用于治疗多发性骨髓瘤（MM）的生物碱盐和U266作为测试MM细胞系证明了这一点。药物VS显示预期的细胞G2-M期停滞。值得注意的是，裸露的金纳米颗粒显示出S期细胞的停滞，这在MM等恶性肿瘤生长缓慢的情况下尤其重要，因为其中大多数细胞仍处于细胞周期的G1期。VS共轭金保留了金纳米颗粒和VS的活性，从而导致凋亡细胞群的协同上升。通常用于治疗多发性骨髓瘤（MM）的生物碱盐和U266作为测试MM细胞系。药物VS显示预期的细胞G2-M期停滞。值得注意的是，裸露的金纳米颗粒显示出S期细胞的停滞，这在MM等恶性肿瘤生长缓慢的情况下尤其重要，因为其中大多数细胞仍处于细胞周期的G1期。VS共轭金保留了金纳米颗粒和VS的活性，从而导致凋亡细胞群的协同上升。通常用于治疗多发性骨髓瘤（MM）的生物碱盐和U266作为测试MM细胞系。药物VS显示预期的细胞G2-M期停滞。值得注意的是，裸露的金纳米颗粒显示出S期细胞的停滞，这在MM等恶性肿瘤生长缓慢的情况下尤其重要，因为其中大多数细胞仍处于细胞周期的G1期。VS共轭金保留了金纳米颗粒和VS的活性，从而导致凋亡细胞群的协同上升。