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Targeted Treatment of Colon Cancer with Aptamer-Guided Albumin Nanoparticles Loaded with Docetaxel
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-09-11 , DOI: 10.2147/ijn.s267177
Zhen Yu 1 , Xundou Li 1 , Jinhong Duan 1 , Xian-Da Yang 1
Affiliation  

Purpose: Chemotherapy of colon cancer needs improvement to mitigate the severe adverse effects (AEs) associated with the cytotoxic drugs. The aim of this study is to develop a novel targeted drug delivery system (TDDS) with practical application potential for colon cancer treatment.
Methods: The TDDS was built by loading docetaxel (DTX) in albumin nanoparticles (NPs) that were functionalized with nucleolin-targeted aptamers (AS1411).
Results: The TDDS (Apt-NPs-DTX) had an average size of 62 nm and was negatively charged with a zeta potential of − 31.2 mV. DTX was released from the albumin NP with a typical sustained release profile. Aptamer-guided NPs were preferentially ingested by nucleolin-expressing CT26 colon cancer cells vs the control cells. In vitro cytotoxicity study showed that Apt-NPs-DTX significantly enhanced the killing of CT26 colon cancer cells. Importantly, compared with non-targeted drug delivery, Apt-NPs-DTX treatment significantly improved antitumor efficacy and prolonged the survival of CT26-bearing mice, without raising systemic toxicity.
Conclusion: The results suggest that Apt-NPs-DTX has potential in the targeted treatment of colon cancer.

Keywords: aptamer, nanoparticles, colon cancer, targeted drug delivery system


中文翻译:

载有多西他赛的适体引导的白蛋白纳米颗粒靶向治疗结肠癌

目的:结肠癌的化疗需要改进以减轻与细胞毒药物相关的严重不良反应 (AE)。本研究的目的是开发一种具有实际应用潜力的结肠癌治疗新型靶向给药系统(TDDS)。
方法: TDDS 是通过将多西紫杉醇 (DTX) 加载到白蛋白纳米颗粒 (NP) 中构建的,这些纳米颗粒用核仁素靶向适体 (AS1411) 进行了功能化。
结果:TDDS (Apt-NPs-DTX) 的平均尺寸为 62 nm,带负电,zeta 电位为 - 31.2 mV。DTX 从白蛋白 NP 中释放出来,具有典型的持续释放曲线。与对照细胞相比,表达核仁素的 CT26 结肠癌细胞优先摄取适体引导的 NP。体外细胞毒性研究表明,Apt-NPs-DTX 显着增强了对 CT26 结肠癌细胞的杀伤作用。重要的是,与非靶向给药相比,Apt-NPs-DTX 治疗显着提高了抗肿瘤功效并延长了携带 CT26 的小鼠的生存期,而不会增加全身毒性。
结论:结果提示Apt-NPs-DTX在结肠癌靶向治疗中具有潜力。

关键词:适体, 纳米粒子, 结肠癌, 靶向给药系统
更新日期:2020-09-11
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