College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan 712-749, South Korea.
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
Carbohydr Polym. 2017 Oct 1;173:57-66. doi: 10.1016/j.carbpol.2017.05.062. Epub 2017 May 20.
In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy.
在本研究中,开发了一种独特的策略,用于开发具有控制释放特性的包含多种治疗剂的纳米载体。在这项研究中,我们展示了葡聚糖硫酸酯-阿霉素(DS-DOX)和海藻酸钠-顺铂(AL-CIS)聚合物-药物复合物的合成,以产生转铁蛋白配体偶联的脂质体。靶向纳米颗粒(TL-DDAC)为纳米级和球形。靶向脂质体在癌细胞中表现出特异性受体介导的内吞作用。与游离药物相比,TL-DDAC 的增强的细胞摄取导致耐药和敏感乳腺癌细胞中的抗癌效果显著提高。具体而言,DOX 和 CIS 的摩尔比为 1:1 时表现出比其他组合更好的治疗性能。基于蒽环类拓扑异构酶 II 抑制剂(DOX)和铂化合物(CIS)的组合导致两种类型的癌细胞中细胞凋亡(早期和晚期)显著增加。总之,用转铁蛋白(TL-DDAC)修饰的基于 DS-DOX 和 AL-CIS 的组合脂质体进行治疗是一种有效的癌症治疗策略。需要在临床相关的动物模型中进一步研究,以证明这种独特策略的治疗效果。