Department of Chemical & Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Singapore 117576, Singapore.
Biomaterials. 2012 Oct;33(30):7519-29. doi: 10.1016/j.biomaterials.2012.06.100. Epub 2012 Jul 17.
We developed a system of nanoparticles of poly(lactide)-d-α-tocopheryl polyethylene glycol succinate (PLA-TPGS) and carboxyl group-terminated TPGS (TPGS-COOH) copolymer blend for multimodality treatment of cancer, which formulated docetaxel for chemotherapy, herceptin for biotherapy and targeting, and iron oxides (IOs) for hyperthermia therapy, which are denoted as MMNPs. It is demonstrated that the MMNPs achieved a significantly higher therapeutic effects than the various combination of the corresponding individual modality treatment NPs and the dual modality treatment NPs due to the synergistic effects among the chemo, bio, and thermo therapies. We further developed a method by employing the concept of NPs IC50, the concentration of the agent-, or agents-loaded nanoparticles that is needed to kill 50% of the cancer cells, to quantitatively access the synergistic effects of the multimodality treatment. It is shown by employing the SK-BR-3 cell line as an in vitro model of the HER2-positive breast cancer that the NPs IC50 is 0.42 mg/mL DCL-NPs plus 1.33 mg/mL Her-NPs plus 0.59 mg/mL IOs-NPs, a total NPs concentration of 2.34 mg/mL for the treatment of a physical mixture of the DCL-NPs, Her-NPs and IOs-NPs at the 1:2:7 weight ratio, while it is only 0.0011 mg/mL for the MMNPs for 24 h, which is 2130 fold more efficient than the physical mixture of the corresponding single modality treatments.
我们开发了一种聚乳酸-α-生育酚聚乙二醇琥珀酸酯（PLA-TPGS）和羧基封端的 TPGS（TPGS-COOH）共聚物混合物的纳米粒子系统，用于癌症的多模式治疗，其中包含多西他赛用于化学治疗、曲妥珠单抗用于生物治疗和靶向治疗以及氧化铁（IOs）用于热疗，这些被称为 MMNPs。结果表明，与相应的各个单模式治疗 NPs 和双模式治疗 NPs 的各种组合相比，MMNPs 实现了更高的治疗效果，因为化学治疗、生物治疗和热疗之间存在协同作用。我们进一步开发了一种方法，通过采用 NPs IC50 的概念，即杀死 50%癌细胞所需的负载药物的纳米粒子的浓度，来定量评估多模式治疗的协同作用。通过使用 SK-BR-3 细胞系作为 HER2 阳性乳腺癌的体外模型表明，NPs IC50 为 0.42 mg/mL DCL-NPs 加 1.33 mg/mL Her-NPs 加 0.59 mg/mL IOs-NPs，总 NPs 浓度为 2.34 mg/mL，用于 DCL-NPs、Her-NPs 和 IOs-NPs 的物理混合物的治疗，重量比为 1:2:7，而 MMNPs 仅为 0.0011 mg/mL，用于 24 h，比相应的单模式治疗的物理混合物效率高 2130 倍。
