Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Drug Dev Ind Pharm. 2022 Feb;48(2):69-78. doi: 10.1080/03639045.2022.2095398. Epub 2022 Jul 4.
Colorectal cancer is one of the most deadly cancers in the world. Docetaxel (DTX) is a potentially important chemotherapeutic agent for the treatment of cancer. Many studies have attempted to improve its bioavailability and efficiency using different nanoparticulate drug delivery systems.
In the current study, PEGylated solid lipid nanoparticles (SLNs) containing DTX were prepared and modified with AS1411 anti-nucleolin aptamers to target nucleoin receptors on colorectal cancer cells.
Nanoparticles were characterized and the morphology was evaluated. studies were investigated on murine colon carcinoma (C26) and Chinese hamster ovary (CHO) cell lines. Then antitumor efficacy and survival analysis were evaluated in mice bearing the C26 tumor model.
Results showed 135-140 nm particle size and about 78% DTX entrapment efficiency for actively targeted samples. PEGylated and aptamer-targeted SLNs containing DTX had the lowest IC (0.28 and 0.11 nM for 3 and 6 h incubation respectively) and higher cellular uptake values in the C26 cell line. Also results demonstrated that PEGylated and aptamer-targeted SLNs containing Docetaxel (Apt-PEG-SLN-DTX) improved antitumor activity and inhibited tumor growth in C26 tumor-bearing mice.
These results suggested that PEGylated and aptamer-targeted SLNs containing DTX exhibited efficient characteristics in tumor inhibitory against murine C26 carcinoma model.
结直肠癌是世界上最致命的癌症之一。多西紫杉醇（DTX）是一种治疗癌症的潜在重要化疗药物。许多研究试图使用不同的纳米颗粒药物传递系统来提高其生物利用度和效率。
在当前的研究中，制备了载有多西紫杉醇的聚乙二醇化固体脂质纳米粒（SLN），并通过 AS1411 核仁素结合适体对其进行修饰，以靶向结直肠癌细胞上的核仁素受体。
对纳米粒进行了表征和形态学评价。研究了载有 DTX 的主动靶向纳米粒在鼠结肠癌细胞（C26）和中国仓鼠卵巢（CHO）细胞系中的抗肿瘤作用。然后，在荷 C26 肿瘤模型的小鼠中进行了抗肿瘤疗效和生存分析。
结果表明，主动靶向样品的粒径为 135-140nm，载药量约为 78%。载有多西紫杉醇的聚乙二醇化和适体靶向 SLN 在 C26 细胞系中具有最低的 IC（分别为 3 小时和 6 小时孵育时为 0.28 和 0.11 nM）和更高的细胞摄取值。此外，结果表明，载有多西紫杉醇的聚乙二醇化和适体靶向 SLN（Apt-PEG-SLN-DTX）提高了抗肿瘤活性，并抑制了 C26 荷瘤小鼠的肿瘤生长。
这些结果表明，载有多西紫杉醇的聚乙二醇化和适体靶向 SLN 对鼠 C26 癌模型具有有效的肿瘤抑制作用。
