Department of Neurosurgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PeerJ. 2024 Sep 13;12:e17979. doi: 10.7717/peerj.17979. eCollection 2024.
This study aims to develop brain-targeted temozolomide (TMZ) nanograins using the biodegradable polymer material PEG-PLA as a carrier. The model drug TMZ was encapsulated within the polymer using targeted nanotechnology. Key characteristics such as appearance, particle size, size distribution, drug loading capacity, release rate, stability, and anti-tumor effects were systematically evaluated through experiments.
Transmission electron microscopy (TEM) and Malvern size analyzer were employed to observe the morphological and particle size features of the TMZ nanospheres at various time points to assess stability. The effects of TMZ nanograins on glioma cell viability and apoptosis were evaluated using MTT assays and flow cytometry.
The targeted TMZ nano-micelles were successfully synthesized. After loading and targeted modifications, the particle size increased from 50.7 to 190 nm, indicating successful encapsulation of TMZ. The average particle size of the nano-micelles remained stable around 145 ± 10 nm at 1 day, 15 days, and 30 days post-preparation. The release rate of the nano-micelles was monitored at 2 h, 12 h, 24 h, and 48 h post-dialysis, ultimately reaching 95.8%. Compared to TMZ alone, the TMZ-loaded PEG-PLA nano-micelles exhibited enhanced cytotoxicity and apoptosis in glioma cells. This was accompanied by increased mitochondrial membrane potential and reactive oxygen species (ROS) levels following treatment with the TMZ nano-micelles.
TMZ-loaded nano-micelles demonstrated a gradual release profile and significantly enhanced inhibitory effects on human glioma U251 cells compared to TMZ alone. The findings suggest that TMZ-loaded PEG-PLA nano-micelles may offer a more effective therapeutic approach for glioma treatment.
本研究旨在使用可生物降解的聚合物材料聚乙二醇-聚乳酸（PEG-PLA）作为载体，开发脑靶向替莫唑胺（TMZ）纳米颗粒。采用靶向纳米技术将模型药物 TMZ 包封在聚合物中。通过实验系统地评估了外观、粒径、粒径分布、载药量、释放率、稳定性和抗肿瘤效果等关键特性。
采用透射电子显微镜（TEM）和马尔文粒径分析仪观察不同时间点 TMZ 纳米球的形态和粒径特征，评估其稳定性。采用 MTT 法和流式细胞术评价 TMZ 纳米颗粒对神经胶质瘤细胞活力和凋亡的影响。
成功合成了靶向 TMZ 纳米胶束。载药和靶向修饰后，粒径从 50.7nm 增加到 190nm，表明 TMZ 成功包封。纳米胶束的平均粒径在制备后 1 天、15 天和 30 天保持在 145±10nm 左右稳定。纳米胶束的释放率在透析后 2h、12h、24h 和 48h 进行监测，最终达到 95.8%。与 TMZ 单药相比，载 TMZ 的 PEG-PLA 纳米胶束在神经胶质瘤细胞中表现出更强的细胞毒性和凋亡作用。这伴随着 TMZ 纳米胶束处理后线粒体膜电位和活性氧（ROS）水平的增加。
与 TMZ 单药相比，载 TMZ 的纳米胶束具有逐渐释放的特性，对人神经胶质瘤 U251 细胞的抑制作用显著增强。研究结果表明，载 TMZ 的 PEG-PLA 纳米胶束可能为治疗神经胶质瘤提供一种更有效的治疗方法。
