Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
J Pharm Sci. 2024 Aug;113(8):2198-2207. doi: 10.1016/j.xphs.2024.02.025. Epub 2024 Mar 1.
The objective of this investigation was to develop a self-assembled, dual-functionalized delivery system that could effectively transport doxorubicin (DOX) to cancer cells through the use of AS1411 aptamer and hyaluronic acid polymer (HA). The ultimate goal is an improved targeting approach for more efficient treatment. The core of this system comprised polyethylenimine (PEI) and FOXM1 aptamer, which was coated by HA. Next, nucleolin targeting aptamers (AS1411) were loaded onto the nanocomplex. Afterward, DOX was added to Aptamers (Apts)-HA-PEI-FOXM1 NPs to create the DOX-AS1411-HA-PEI-FOXM1 NPs for better treatment of cancer cells. The cytotoxic effect of the nanocomplex on L929, 4T1, and A549 cells showed that cell mortality in target cancer cells (4T1 and A549) was considerably enhanced compared to nontarget cells (L929, normal cells). The findings from the flow cytometry analysis and fluorescence imaging demonstrated the cellular absorption of DOX-Apts-HA-PEI-FOXM1 NPs in target cells was significantly enhanced when compared to L929 cells. Furthermore, in vivo antitumor study exhibited that DOX-Apts-HA-PEI-FOXM1 NPs rendered specific tumor accumulation and increasing of the anti-tumor effects.
本研究旨在开发一种自组装的双功能递药系统,该系统能够通过使用 AS1411 适体和透明质酸聚合物(HA)将阿霉素(DOX)有效递送至癌细胞。最终目标是改善靶向方法,以实现更有效的治疗。该系统的核心由聚乙烯亚胺(PEI)和 FOXM1 适体组成,其表面涂覆有 HA。接下来,将核仁素靶向适体(AS1411)装载到纳米复合物上。然后,将 DOX 添加到适体(Apts)-HA-PEI-FOXM1 NPs 中,以形成 DOX-AS1411-HA-PEI-FOXM1 NPs,从而更好地治疗癌细胞。纳米复合物对 L929、4T1 和 A549 细胞的细胞毒性作用表明,与非靶细胞(L929,正常细胞)相比,靶癌细胞(4T1 和 A549)中的细胞死亡率明显提高。流式细胞术分析和荧光成像的结果表明,与 L929 细胞相比,DOX-Apts-HA-PEI-FOXM1 NPs 在靶细胞中的细胞摄取明显增强。此外,体内抗肿瘤研究表明,DOX-Apts-HA-PEI-FOXM1 NPs 具有特异性肿瘤蓄积和增强抗肿瘤作用。