Dutta Dipranil, Pajaniradje Sankar, Nair Anjali Suresh, Chandramohan Sathyapriya, Bhat Suhail Ahmad, Manikandan E, Rajagopalan Rukkumani
Department of Biochemistry and Molecular Biology, School of Life Science, Pondicherry University, Puducherry 605014, India.
Centre for Nano Sciences and Technology, Madanjeet School of Green Energy Technologies, Pondicherry University, Puducherry 605014, India.
Int J Biol Macromol. 2024 Dec;282(Pt 5):136990. doi: 10.1016/j.ijbiomac.2024.136990. Epub 2024 Nov 4.
Natural compounds like Curcumin with anti-cancer, anti-inflammatory and anti-bacterial properties are good target for drug development but its poor aqueous solubility, bioavailability, and low retention properties makes it a poor drug candidate in clinical settings. Here in this study, we have used an indole curcumin analogue (ICA) that has better bioavailability and enhanced permeability and retention (EPR) effect than curcumin. To make an active targeting drug we have designed folic acid conjugated chitosan-based nanoparticles encapsulating Indole curcumin analogue (CS-FA-ICA-np). The physical characteristics of CS-FA-ICA-np were evaluated by DLS, SEM, FTIR, XPS, XRD and TGA. Anti-cancer activity was analyzed using MTT, Fluorescence staining, Flow cytometry, comet assay, DNA fragmentation assay, wound healing, gelatin zymography, chick chorioallantoic membrane (CAM) assay and hemolysis assay. The size of CS-FA-ICA-nps were found to be 111 nm, and spherical in shape as observed in SEM. In-vitro assays show that CS-FA-ICA np has IC of 90 μg/mL in MDA-MB-231, increases ROS concentration, arrests cell cycle in G2-M phase, reduces matrix metalloproteinase-9 (MMP-9) activity and initiates apoptosis in cancer cells. Our results indicate that encapsulation of ICA increases its anti-cancer effect, drug stability, enhanced drug delivery to cancer microenvironment.
姜黄素等具有抗癌、抗炎和抗菌特性的天然化合物是药物开发的良好靶点，但其水溶性差、生物利用度低以及保留特性不佳，使其在临床环境中成为不佳的药物候选物。在本研究中，我们使用了一种吲哚姜黄素类似物（ICA），它比姜黄素具有更好的生物利用度以及增强的渗透滞留（EPR）效应。为了制备一种主动靶向药物，我们设计了包裹吲哚姜黄素类似物的叶酸共轭壳聚糖基纳米颗粒（CS-FA-ICA-np）。通过动态光散射（DLS）、扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线光电子能谱（XPS）、X射线衍射（XRD）和热重分析（TGA）对CS-FA-ICA-np的物理特性进行了评估。使用MTT法、荧光染色、流式细胞术、彗星试验、DNA片段化试验、伤口愈合试验、明胶酶谱法、鸡胚绒毛尿囊膜（CAM）试验和溶血试验分析了其抗癌活性。如在扫描电子显微镜中观察到的，CS-FA-ICA-nps的尺寸为111nm，呈球形。体外试验表明，CS-FA-ICA np在MDA-MB-231细胞中的半数抑制浓度（IC）为90μg/mL，可增加活性氧（ROS）浓度，使细胞周期停滞在G2-M期，降低基质金属蛋白酶-9（MMP-9）活性并引发癌细胞凋亡。我们的结果表明，ICA的包封增加了其抗癌效果、药物稳定性，并增强了药物向癌微环境的递送。
