Department of Pharmacy (pharmaceutics), Baghdad College of Medical Sciences, 10047, Baghdad, Iraq.
Department of Pharmaceutics, College of Pharmacy, Al-Nahrain university, 10072, Baghdad, Iraq.
Chem Biodivers. 2024 Oct;21(10):e202401106. doi: 10.1002/cbdv.202401106. Epub 2024 Sep 9.
Lung cancer, as the leading cause of death among other types of cancer, has a high rate of incidence throughout the world. Although conventional modalities, like chemotherapy, have been applied for the inhibition of this cancer, they have not led to the suppression of lung cancer owing to their deficiencies. Thus, we developed a novel polylactic-co-glycolic acid (PLGA)-polyamidoamine G4 (PAMAM G4)-polycaprolactone (PCL) nanocarrier for efficient delivery of curcumin (Cur) to A549 lung cancer cells. The synthesized nanocarrier was characterized by applying analytical techniques, FT-IR, DLS, TEM, and TGA. Successful synthesis, nano-size diameter (40-80 nm), near neutral surface charge (8.0 mV), and high drug entrapment (11.5 %) were measured for the nanocarrier. Controlled (about 5 folds within first 2 h) and pH-sensitive (2-3 folds faster within first hours) Cur release observed for PLGA-PAMAM-PCL-Cur. Cell viability test (MTT assay) indicated the high capability of nanocarrier in suppression of A549 cancer cells (21 % viability after 24 h of treatment with 200 nM) while did not result in toxicity on MSC normal cells. The IC observed for 50 nM at 24 h of post-treatment in A549 cells. The qRT-PCR technique indicated inducing the expression of apoptotic genes (Caspase9 and Bax) by 6-8 folds and suppressing anti-apoptotic gene (Bcl2) by 7 folds. ROS considerably increased in cancer cells as well. This nanocarrier would be a promising drug delivery system against lung cancer.
肺癌是其他癌症类型中导致死亡的主要原因,在全球范围内发病率很高。尽管化疗等传统方法已被用于抑制这种癌症,但由于其缺陷,并未抑制肺癌的发生。因此,我们开发了一种新型的聚乳酸-羟基乙酸共聚物(PLGA)-聚酰胺胺 G4(PAMAM G4)-聚己内酯(PCL)纳米载体,用于高效递送至 A549 肺癌细胞的姜黄素(Cur)。通过应用分析技术、FT-IR、DLS、TEM 和 TGA 对合成的纳米载体进行了表征。成功合成、纳米尺寸直径(40-80nm)、接近中性表面电荷(8.0mV)和高药物包封率(11.5%)对纳米载体进行了测量。观察到 Cur 的控制释放(前 2h 内约 5 倍)和 pH 敏感性释放(前几小时内快 2-3 倍)。PLGA-PAMAM-PCL-Cur 的细胞活力测试(MTT 测定)表明纳米载体在抑制 A549 癌细胞方面具有高能力(用 200nM 处理 24 小时后细胞活力为 21%),而对 MSC 正常细胞没有毒性。在 A549 细胞中,处理后 24 小时观察到的 IC 为 50nM。qRT-PCR 技术表明,促凋亡基因(Caspase9 和 Bax)的表达诱导增加了 6-8 倍,抗凋亡基因(Bcl2)的表达抑制了 7 倍。ROS 在癌细胞中也明显增加。这种纳米载体将是一种有前途的治疗肺癌的药物递送系统。