Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
Flow Cytometry Core, Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Int J Biol Macromol. 2023 Apr 30;235:123827. doi: 10.1016/j.ijbiomac.2023.123827. Epub 2023 Feb 27.
Colon cancer (CRC) is the second leading cause of death and the third most diagnosed cancer worldwide. Although curcumin (CUR) has demonstrated a potent anticancer activity, it is characterized by its poor solubility, low bioavailability, and instability. This study is a projection from a previous investigation where CUR and succinylated CUR (CUR.SA) were separately encapsulated in mannosylated-chitosan nanoparticles (CM-NPs) to form CUR-NPs and CUR.SA-NPs, respectively. Here, we aim to assess the anti-CRC activity of these two nanoformulations. Cytotoxicity studies using CCK-8 assay indicated that both CUR-NPs and CUR.SA-NPs have a dose and time-dependent toxicity towards CRC human cell-lines (HCT116 and SW480), and more cytotoxic compared to free CUR or CUR-SA in a time-dependent manner. A significant induction of early and late apoptosis in the CUR-NPs and CUR.SA-NPs treated CRC cell lines compared to untreated cells was observed. Western blotting analyses confirmed the induction of apoptosis through activation of Caspase signaling compared to untreated cells. Based on the physicochemical properties of CUR-NPs and CUR.SA-NPs along with the data from the in vitro studies, we may conclude these nanoparticle formulations hold very promising attributes, worthy of further investigations for its role in the management of CRC.
结肠癌(CRC)是全球第二大死亡原因和第三大被诊断出的癌症。尽管姜黄素(CUR)已显示出强大的抗癌活性,但它的溶解度低、生物利用度低且不稳定。本研究是对先前一项研究的预测,其中分别将 CUR 和琥珀酰化 CUR(CUR.SA)包封在甘露糖化壳聚糖纳米粒子(CM-NPs)中,形成 CUR-NPs 和 CUR.SA-NPs。在这里,我们旨在评估这两种纳米制剂的抗 CRC 活性。使用 CCK-8 测定的细胞毒性研究表明,CUR-NPs 和 CUR.SA-NPs 对 CRC 人细胞系(HCT116 和 SW480)具有剂量和时间依赖性毒性,并且与游离 CUR 或 CUR-SA 相比,在时间依赖性方面具有更高的细胞毒性。与未处理的细胞相比,在 CUR-NPs 和 CUR.SA-NPs 处理的 CRC 细胞系中观察到早期和晚期凋亡的显著诱导。Western blot 分析证实,与未处理的细胞相比,通过 Caspase 信号的激活诱导了细胞凋亡。基于 CUR-NPs 和 CUR.SA-NPs 的物理化学性质以及体外研究的数据,我们可以得出结论,这些纳米粒子制剂具有非常有前途的特性,值得进一步研究其在 CRC 管理中的作用。