Mohajeri Sahar, Yaghoubi Hashem, Bourang Shima, Noruzpour Mehran
Department of Chemistry, Ard.C., Islamic Azad University, Ardabil, Iran.
Department of Biology, Ard.C., Islamic Azad University, Ardabil, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 27. doi: 10.1007/s00210-025-04381-8.
The targeted delivery of nucleic acids and drugs via nanoparticles to damaged cells remains a significant challenge in cancer treatment. This study focused on the bipolar copolymer FeO/chitosan/polycaprolactone (PCL)/polyethylene glycol (PEG)-hyaluronic acid (HA) nanocapsules designed to enhance drug delivery to CD receptor-expressing MCF-7 cancer cells. These nanoparticles integrate iron oxide, hydrophilic PEG, biodegradable PCL, cationic chitosan, and hyaluronic acid. The physicochemical properties of the nanoparticles were investigated and confirmed via Fourier transform infrared (FTIR) spectroscopy and differential thermogravimetric (DTG) analysis. After paclitaxel (PTX) and siRNA-FAM loading, the zeta potential, dynamic light scattering (DLS), and scanning electron microscopy (SEM) confirmed the successful synthesis and appropriate structural properties of the nanocapsules. The nanocapsules were measured at approximately 230 nm with a zeta potential of - 2.5 mV. Release studies at pH 5 and 7.4 demonstrated that a lower pH significantly increased the release rates of PTX and siRNA-FAM. Electrophoretic analysis indicated that the nanocapsule coating (controlled-release nanoprotective coating) protected these agents from plasma degradation. An evaluation of the magnetic properties via a vibrating sample magnetometer (VSM) revealed that the iron oxide nanoparticles exhibited desirable magnetic characteristics, with values decreasing from 42.5 to 16.8 emu/g upon encapsulation. Cytotoxicity assessments via the MTT assay indicated the low toxicity (IC = 492.7 μg/mL) of the nanocapsules to the MCF-7 cell line. Flow cytometry revealed effective targeted gene transfer, with significant pre- and post-apoptosis rates (18.14% and 15.65%, respectively) for the FeO/chitosan/PCL/PEG-HA/PTX treatment. The agarose gel and fluorescence microscopy results confirmed the superior gene transfer efficiency of the FeO/chitosan/PCL/PEG-HA/siRNA-FAM nanocapsules compared with the controls, which was attributed to their stability and the presence of hyaluronic acid groups. This study presents the first application of these nanocapsules for gene and drug delivery.
通过纳米颗粒将核酸和药物靶向递送至受损细胞仍然是癌症治疗中的一项重大挑战。本研究聚焦于双极共聚物FeO/壳聚糖/聚己内酯（PCL）/聚乙二醇（PEG）-透明质酸（HA）纳米胶囊，其设计目的是增强药物向表达CD受体的MCF-7癌细胞的递送。这些纳米颗粒整合了氧化铁、亲水性PEG、可生物降解的PCL、阳离子壳聚糖和透明质酸。通过傅里叶变换红外（FTIR）光谱和差示热重（DTG）分析对纳米颗粒的物理化学性质进行了研究和确认。在负载紫杉醇（PTX）和siRNA-FAM后，zeta电位、动态光散射（DLS）和扫描电子显微镜（SEM）证实了纳米胶囊的成功合成及其合适的结构性质。测得纳米胶囊的粒径约为230 nm，zeta电位为 - 2.5 mV。在pH 5和7.4条件下的释放研究表明，较低的pH值显著提高了PTX和siRNA-FAM的释放速率。电泳分析表明，纳米胶囊涂层（控释纳米保护涂层）可保护这些药物不被血浆降解。通过振动样品磁强计（VSM）对磁性进行评估，结果显示氧化铁纳米颗粒表现出理想的磁性特征，封装后其值从42.5降至16.8 emu/g。通过MTT法进行的细胞毒性评估表明，纳米胶囊对MCF-7细胞系的毒性较低（IC = 492.7 μg/mL）。流式细胞术显示基因转移有效，FeO/壳聚糖/PCL/PEG-HA/PTX处理的细胞凋亡前和凋亡后率分别显著为18.14%和15.65%。琼脂糖凝胶和荧光显微镜结果证实，与对照组相比，FeO/壳聚糖/PCL/PEG-HA/siRNA-FAM纳米胶囊具有更高的基因转移效率，这归因于其稳定性和透明质酸基团的存在。本研究首次展示了这些纳米胶囊在基因和药物递送方面的应用。
