Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Nanomedicine. 2014 Jan;10(1):99-107. doi: 10.1016/j.nano.2013.07.009. Epub 2013 Jul 24.
Trastuzumab-conjugated pH-sensitive double emulsion nanocapsules (DENCs) stabilized by a single-component Poly (vinyl alcohol) (PVA) with magnetic nanoparticles can be fabricated through a two-step double emulsion process; these nanocapsules can be used to encapsulate hydrophilic doxorubicin (Dox) and hydrophobic paclitaxel (PTX) simultaneously. When PMASH was attached to the shell of the DENCs, enhanced dual drug release of PTX/Dox was detected, specifically in intracellular acidic pH environments. The targeting ability of these Trastuzumab-conjugated DENCs was demonstrated with confocal images, which revealed a significantly elevated cellular uptake in HER-2 overexpressing SkBr3 cells. More importantly, an intravenous injection of this co-delivery system followed by magnetic targeting (MT) chemotherapy suppressed cancer growth in vivo more efficiently than the delivery of either PTX or Dox alone. The integration of the functionalities makes this combination therapy system a powerfully new tool for in vitro/in vivo cancer therapy, especially for in HER-2 positive cancers.
Trastuzumab-conjugated pH-sensitive nanocapsules were used in this study for simultaneous targeted delivery of hydrophobic (PTX) and hydrophilic (Dox) anti-cancer agents to HER-2 positive cancer cells. Additional use of magnetic targeting demonstrated superior efficacy of this delivery system compared to PTX or Dox alone.
通过两步双乳液工艺可制备由单一组分聚乙烯醇(PVA)稳定的曲妥珠单抗偶联 pH 敏感的双乳液纳米胶囊(DENCs),这些纳米胶囊可同时包封亲水性阿霉素(Dox)和疏水性紫杉醇(PTX)。当 PMASH 连接到 DENCs 的外壳上时,检测到 PTX/Dox 的双重药物释放增强,特别是在细胞内酸性 pH 环境中。通过共聚焦图像证明了这些曲妥珠单抗偶联的 DENCs 的靶向能力,这些图像显示在过表达 HER-2 的 SkBr3 细胞中,细胞摄取率显著提高。更重要的是,与单独给予 PTX 或 Dox 相比,这种共递药系统的静脉注射联合磁靶向(MT)化疗更有效地抑制了体内肿瘤的生长。功能的整合使这种联合治疗系统成为体外/体内癌症治疗的有力新工具,特别是在 HER-2 阳性癌症中。
在这项研究中,曲妥珠单抗偶联的 pH 敏感纳米胶囊用于将亲脂性(PTX)和亲水性(Dox)抗癌药物同时靶向递送至 HER-2 阳性癌细胞。额外使用磁靶向证明了与单独使用 PTX 或 Dox 相比,该递药系统具有更好的疗效。