Department of Molecular Science and Technology, Ajou University , 5 Wonchon, Yeongtong, Suwon, 443-749, Republic of Korea.
Mol Pharm. 2013 Feb 4;10(2):685-93. doi: 10.1021/mp300480v. Epub 2012 Dec 28.
Combination chemotherapy using more than two therapeutic agents with different modes of action is a promising strategy that can be used to enhance the therapeutic efficacy of cancer treatment, even though it is a complicated treatment modality. The aim of this study was to investigate how a novel multidrug nanocarrier is effective for combination chemotherapy in vitro and, more specifically, whether combined agents with different modes of action and physicochemical properties show synergistic cytotoxicity with the use of this nanocarrier. A heparin-Pluronic (Hep-Pr) nanogel encapsulating both paclitaxel and DNase was shown to be efficient for intracellular delivery with respect to size, encapsulation efficiency, and intracellular uptake/fates. As a result of these properties, a Hep-Pr nanogel combined with paclitaxel and DNase exhibited a dose-dependent synergistic cytotoxicity compared to single drug and free-drug treatments, whose combination indices were 0.93 and 0.45 at higher concentrations (250 and 500 μg/mL). Therefore, Hep-Pr nanogels have the potential to deliver multitherapeutic agents with different characteristics and thereby enhance the therapeutic efficacy of combination cancer chemotherapy.
联合化疗使用两种以上具有不同作用模式的治疗剂是一种很有前途的策略，可用于提高癌症治疗的疗效，尽管它是一种复杂的治疗方式。本研究的目的是研究新型多药纳米载体在体外联合化疗中的有效性，更具体地说，就是研究具有不同作用模式和理化性质的联合药物是否与该纳米载体联合使用具有协同细胞毒性。肝素-泊洛沙姆（Hep-Pr）纳米凝胶可以有效地将紫杉醇和 DNase 包封在内，在尺寸、包封效率和细胞内摄取/命运方面具有优势。由于这些特性，与单药和游离药物治疗相比，Hep-Pr 纳米凝胶与紫杉醇和 DNase 的联合具有剂量依赖性协同细胞毒性，在较高浓度（250 和 500 μg/mL）时的组合指数分别为 0.93 和 0.45。因此，Hep-Pr 纳米凝胶有可能递送具有不同特征的多种治疗药物，从而增强联合癌症化疗的疗效。
