Shen Chiung-Chyi, Yang Meng-Yin, Hsieh Wan-Yu, Tsay Gregory J, Yang Yi-Chin, Huang Yu-Fen, Liu Szu-Yuan, Lai Chih-Ming, Lee Chung Hsin, Tang Cheng-Ming, Hung Huey-Shan
Department of Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung 407219, Taiwan R.O.C.
Department of Physical Therapy, Hung Kuang University, Taichung 433304, Taiwan, R.O.C.
ACS Nanosci Au. 2025 Apr 18;5(3):165-183. doi: 10.1021/acsnanoscienceau.5c00004. eCollection 2025 Jun 18.
This study examined the effects of berberine, a bioactive alkaloid, on the apoptosis, proliferation, migration, and oxidative stress of DBTRG brain cancer cells and evaluated its potential when incorporated into a nanoparticle-mediated drug delivery system. DBTRG cells treated with 0.5, 1, 5, or 10 μg/mL of berberine for 48 h showed increased apoptosis through both intrinsic and extrinsic pathways, as evidenced by elevated annexin V+/propidium iodide- cells relative to untreated controls. Berberine effectively reduced cell proliferation by inducing cell cycle arrest at G1 and G2/M phases. It also inhibited cell migration by downregulating matrix metalloproteinases and modifying the cytoskeletal structure, and alleviated oxidative stress by enhancing antioxidant enzyme activity and lowering reactive oxygen species production. To overcome the limitations of berberine's low bioavailability, a nanoparticle-based delivery system was developed. The gold-collagen-berberine (Au-Col-BB) nanocarrier was characterized using UV-vis spectrophotometry, Fourier-transform infrared spectroscopy, dynamic light scattering, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. Au-Col-BB nanoparticles were engineered to enhance berberine's loading capacity and therapeutic efficacy. These nanoparticles entered DBTRG cells via endocytosis and progressed through the endosome-lysosome pathway, which significantly increased cellular uptake and therapeutic effectiveness. Annexin V/propidium iodide staining and cell cycle analysis demonstrated that Au-Col-BB nanoparticles promoted DBTRG cell apoptosis. The sub-G1 phase cell population increased by 19.4% ( < 0.001) compared to controls, while the S phase population decreased by 5.6% ( < 0.001), indicating enhanced apoptotic activity and reduced proliferation. In vivo analysis via retroorbital sinus injection of Au-Col-BB into BALB/c mice ( = 5) confirmed the nanoparticles' structural integrity and safety, as well as efficient accumulation in brain tissue. These findings underscore berberine's potential as an anticancer agent, particularly when delivered through a nanoparticle-based system to address the challenges of limited bioavailability and achieve targeted delivery to cancer cells.
本研究考察了生物活性生物碱黄连素对DBTRG脑癌细胞凋亡、增殖、迁移及氧化应激的影响，并评估了其在纳米颗粒介导的药物递送系统中的潜力。用0.5、1、5或10μg/mL黄连素处理DBTRG细胞48小时后，通过内源性和外源性途径均显示凋亡增加，相对于未处理的对照，膜联蛋白V+/碘化丙啶-细胞增加证明了这一点。黄连素通过诱导细胞周期停滞在G1和G2/M期有效降低细胞增殖。它还通过下调基质金属蛋白酶和改变细胞骨架结构来抑制细胞迁移，并通过增强抗氧化酶活性和降低活性氧产生来减轻氧化应激。为了克服黄连素生物利用度低的局限性，开发了一种基于纳米颗粒的递送系统。使用紫外可见分光光度法、傅里叶变换红外光谱法、动态光散射法、能量色散X射线光谱法、X射线光电子能谱法和扫描电子显微镜对金-胶原蛋白-黄连素（Au-Col-BB）纳米载体进行了表征。Au-Col-BB纳米颗粒经设计以提高黄连素的负载能力和治疗效果。这些纳米颗粒通过内吞作用进入DBTRG细胞，并通过内体-溶酶体途径，这显著增加了细胞摄取和治疗效果。膜联蛋白V/碘化丙啶染色和细胞周期分析表明，Au-Col-BB纳米颗粒促进了DBTRG细胞凋亡。与对照相比，亚G1期细胞群体增加了19.4%（<0.001），而S期群体减少了5.6%（<0.001），表明凋亡活性增强且增殖减少。通过眶后窦向BALB/c小鼠（n=5）注射Au-Col-BB进行的体内分析证实了纳米颗粒的结构完整性和安全性，以及在脑组织中的有效积累。这些发现强调了黄连素作为抗癌剂的潜力，特别是当通过基于纳米颗粒的系统递送时，以应对生物利用度有限的挑战并实现对癌细胞的靶向递送。
