School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan; Drug Research Center, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.
Int J Biol Macromol. 2024 Nov;281(Pt 4):136651. doi: 10.1016/j.ijbiomac.2024.136651. Epub 2024 Oct 16.
Ovarian cancer is a leading gynecological cancer globally. This study aimed to develop hyaluronic acid-modified polyethylene glycol conjugated zein nanoparticles (zein-PEG/HA NPs) to enhance paclitaxel (PTX) cytotoxicity in SKOV3 ovarian cancer cells. Zein-PEG, with its amphiphilic nature, self-assembled into micelles to encapsulate the hydrophobic PTX, while the PEG shell retained micelle stability and hemolytic resistance. PTX@zein-PEG micelles (17.2 ± 0.3 mV) were complexed with negatively charged HA through electrostatic interactions, resulting in PTX@zein-PEG/HA NPs with a negative zeta potential of -15.3 ± 1.1 mV. Cellular uptake of fluorescent zein-PEG/HA NPs was higher than zein-PEG micelles in CD44-overexpressing SKOV3 cells. Additionally, PTX@zein-PEG/HA NPs demonstrated significantly greater cytotoxicity than free PTX and PTX@zein-PEG micelles, with IC values reduced by 6.13-fold and 3.58-fold, respectively. PTX@zein-PEG/HA NPs induced the highest expression levels of apoptotic proteins, particularly PARP, in SKOV3 cells compared to PTX@zein-PEG NPs and free PTX. In summary, PTX@zein-PEG/HA NPs demonstrated potential as a delivery system for PTX in ovarian cancer.
卵巢癌是全球主要的妇科癌症。本研究旨在开发透明质酸修饰的聚乙二醇偶联玉米醇溶蛋白纳米粒（zein-PEG/HA NPs），以增强 SKOV3 卵巢癌细胞中紫杉醇（PTX）的细胞毒性。玉米醇溶蛋白具有两亲性，自组装成胶束以包裹疏水性的 PTX，而 PEG 壳则保持胶束的稳定性和抗溶血能力。PTX@zein-PEG 胶束（17.2±0.3 mV）通过静电相互作用与带负电荷的 HA 复合，形成负 zeta 电位为-15.3±1.1 mV 的 PTX@zein-PEG/HA NPs。在 CD44 过表达的 SKOV3 细胞中，荧光标记的 zein-PEG/HA NPs 的细胞摄取量高于 zein-PEG 胶束。此外，PTX@zein-PEG/HA NPs 对 SKOV3 细胞的细胞毒性明显大于游离 PTX 和 PTX@zein-PEG 胶束，IC 值分别降低了 6.13 倍和 3.58 倍。PTX@zein-PEG/HA NPs 在 SKOV3 细胞中诱导的凋亡蛋白表达水平，尤其是 PARP，明显高于 PTX@zein-PEG NPs 和游离 PTX。综上所述，PTX@zein-PEG/HA NPs 有望成为卵巢癌中 PTX 的递送系统。
