Chemistry Department, Faculty of Science, Damietta University, Damietta, 34517, Egypt.
Cancer Chemother Pharmacol. 2019 Apr;83(4):649-658. doi: 10.1007/s00280-019-03770-0. Epub 2019 Jan 16.
Searching for novel anticancer therapeutics which are effective and primarily less toxic is urgently needed. Drug encapsulation provides more protection of drug within the body with more stable drug circulation levels thus avoiding drug peak-related adverse effects. We aimed first to develop and characterize a nano-particulate drug delivery system using poly(lactic-co-glycolic acid) (PLGA) for the new compound N-butylpyridoquinoxaline 1,4-dioxide (NBPQD), and second to investigate its anticancer effect and the probable mechanism.
NBPQD-PLGA nano-particles were prepared and their shape, size, zeta potential, encapsulation efficiency (EE%), drug loading (DL%), drug release, anticancer activity against six human cancer cell lines, DNA binding ability, and flow cytometric analyses of apoptosis, cell cycle and caspase-3 activity were investigated.
NBPQD-PLGA nano-particles were spherical with diameter around 54 nm. Zeta potential, EE%, and DL% values were - 20.4 mV, 88% and 21.8%, respectively. Nano-particles exhibited higher marked anticancer activities (much lower ICs) and changed the anticancer potency pattern towards all the studied cell lines compared to free NBPQD with superior potency against colorectal carcinoma (HCT-116, IC of 12.2 µg/mL). NBPQD-PLGA acts by induction of cancer cell apoptosis through oxidative stress, DNA damage, and activating a caspase-3 signaling pathway.
寻找有效且毒性较低的新型抗癌治疗药物迫在眉睫。药物包封提供了更多的药物保护，使体内药物循环水平更稳定，从而避免与药物峰值相关的不良反应。我们的目的首先是使用聚（乳酸-共-乙醇酸）（PLGA）开发和表征新化合物 N-丁基吡啶并[2,3-d]恶嗪-1,4-二氧化物（NBPQD）的纳米颗粒药物递送系统，其次是研究其抗癌作用和可能的机制。
制备 NBPQD-PLGA 纳米颗粒，并对其形状、大小、Zeta 电位、包封效率（EE%）、载药量（DL%）、药物释放、对六种人癌细胞系的抗癌活性、DNA 结合能力以及流式细胞术分析细胞凋亡、细胞周期和 caspase-3 活性进行研究。
NBPQD-PLGA 纳米颗粒呈球形，直径约为 54nm。Zeta 电位、EE%和 DL%值分别为-20.4mV、88%和 21.8%。纳米颗粒表现出更高的抗癌活性（更低的 IC 值），并改变了所有研究细胞系的抗癌效力模式，与游离 NBPQD 相比，对结直肠癌细胞（HCT-116，IC 为 12.2μg/mL）具有更强的效力。NBPQD-PLGA 通过诱导癌细胞凋亡、氧化应激、DNA 损伤和激活 caspase-3 信号通路来发挥作用。
