Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan, China.
Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan, China.
Biomater Sci. 2016 Nov 15;4(12):1742-1753. doi: 10.1039/c6bm00444j.
The development of a controlled-release drug delivery system has been an important objective for cancer therapy. To achieve the goal of sustained drug release for preventing the biotoxicity of platinum drugs, oxaliplatin was encapsulated into PEGylated multiwalled carbon nanotubes (MWNTs) decorated with superparamagnetic iron oxide (SPIO) for magnetic resonance imaging (MRI). The superparamagnetic properties and purification of SPIO/MWNT composites were achieved by annealing treatment during the fabrication process; the better hydrophilicity and biocompatibility were also accomplished subsequently after modification with polyethylene glycol (PEG). Oxa/MagMWNT-PEG 7 presented the ability of sustained release, as only 36.25% of loaded oxaliplatin leaked within 12 h and 55.48% lasted over 144 h. An in vitro study revealed that compared with free oxaliplatin and Oxa/MagMWNT 8, Oxa/MagMWNT-PEG 7 showed a slightly decreased cytotoxic effect when the cell viability was assessed at 12 and 24 h; however, a drastic enhancement in cytotoxicity was observed at 96 h. Platinum-DNA quantification on HCT116 cells showed that the internalization of oxaliplatin lasted up to 96 h, which was due to the sustained release of nanomedicine. An in vivo study showed that the nanomedicine-treated group exhibited effective antitumor efficacy similar to the free drug-treated group, but without inducing death in mice. After intravenous administration, the T-weighted MRI signal revealed that Oxa/MagMWNT-PEG7 had an excellent MRI enhancement in the tumor region. This SPIO-decorated MWNT composite encapsulated with antitumor drugs could potentially be useful for treatments, such as cancer therapy and MRI.
控释药物递送系统的开发一直是癌症治疗的一个重要目标。为了实现持续释放药物以防止铂类药物的生物毒性的目标,奥沙利铂被包封在聚乙二醇化多壁碳纳米管(MWNTs)中,该 MWNTs 用超顺磁性氧化铁(SPIO)修饰以用于磁共振成像(MRI)。在制造过程中通过退火处理实现了 SPIO/MWNT 复合材料的超顺磁性和纯化;随后通过与聚乙二醇(PEG)修饰也实现了更好的亲水性和生物相容性。Oxa/MagMWNT-PEG7 具有持续释放的能力,因为只有 36.25%的负载奥沙利铂在 12 小时内泄漏,而 55.48%持续超过 144 小时。体外研究表明,与游离奥沙利铂和 Oxa/MagMWNT8 相比,Oxa/MagMWNT-PEG7 在细胞活力评估为 12 和 24 小时时表现出稍低的细胞毒性作用;然而,在 96 小时时观察到细胞毒性的急剧增强。对 HCT116 细胞的铂-DNA 定量表明,奥沙利铂的内化持续到 96 小时,这是由于纳米药物的持续释放。体内研究表明,纳米药物治疗组表现出与游离药物治疗组相似的有效抗肿瘤功效,但不会导致小鼠死亡。静脉给药后,T 加权 MRI 信号显示 Oxa/MagMWNT-PEG7 在肿瘤区域具有极好的 MRI 增强。这种用抗肿瘤药物包封的 SPIO 修饰的 MWNT 复合材料可能对癌症治疗和 MRI 等治疗有用。