State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China; Graduate School, University of Chinese Academy of Sciences, 100049, Beijing, China.
State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China.
Carbohydr Polym. 2018 Sep 1;195:311-320. doi: 10.1016/j.carbpol.2018.04.087. Epub 2018 Apr 24.
Chemotherapy-based treatment for cancer has made great progress in the past decades. However, there is still a big challenge for the treatment of lung cancer. Herein, a multifunctional nanocarrier was developed through electrostatic interaction between the fluorescent gold nanocluster-conjugated chitosan and the nucleolin targeting AS1411 aptamer. Then methotrexate was loaded into the multifunctional nanocarrier through hydrophobic interaction to obtain the nanodrug carrier systems. The prepared nanodrug carrier systems have an average nanoparticle size of 200 nm with 13.8% drug loading efficiency. The drug release is pH-dependent. The in vitro results demonstrated that the nanodrug carrier systems were selectively taken up by cancer cells in a time-dependent manner and exhibited significantly enhanced anticancer activity in a model of lung cancer A549 cells. The in vivo results showed that intravenous administration of nanodrug carrier systems into BALB/c mice led to accumulation of methotrexate at the tumor site and significantly inhibited the tumor growth but without overt toxicity. The present study suggests that the prepared multifunctional nanocarrier can be used as an effective drug delivery system for anticancer drugs and exhibits great potential in clinical applications.
在过去几十年中，基于化疗的癌症治疗取得了重大进展。然而，肺癌的治疗仍然面临着巨大的挑战。在此，通过荧光金纳米簇偶联壳聚糖与核仁素靶向 AS1411 适体之间的静电相互作用，开发了一种多功能纳米载体。然后通过疏水相互作用将甲氨蝶呤载入多功能纳米载体中，得到纳米药物载体系统。所制备的纳米药物载体系统的平均纳米颗粒尺寸为 200nm，载药效率为 13.8%。药物释放呈 pH 依赖性。体外结果表明，纳米药物载体系统能够被癌细胞以时间依赖的方式选择性摄取，并在肺癌 A549 细胞模型中表现出显著增强的抗癌活性。体内结果表明，将纳米药物载体系统静脉注射到 BALB/c 小鼠体内，导致甲氨蝶呤在肿瘤部位聚集，并显著抑制肿瘤生长，但无明显毒性。本研究表明，所制备的多功能纳米载体可用作抗癌药物的有效药物递送系统，在临床应用中具有巨大潜力。
