Ou Zemin, Li Xinjian, You Yun, Liu Dewen, Wang Jinyu
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 10700, China.
ACS Omega. 2023 Mar 22;8(13):12259-12267. doi: 10.1021/acsomega.2c08265. eCollection 2023 Apr 4.
Glioblastoma is considered the most fatal malignant brain tumor that starts from the central nervous system (CNS), where the blood-brain barrier (BBB) remains the biggest challenge for active targeting of drugs in malignant brain tumor. Thereby, we have designed a paclitaxel PTX@ANG/FA-NPs hybrid novel nanodrug delivery system that can overcome the clinical BBB. The structural and morphological characterization of PTX@ANG/FA-NPs confirmed successful synthesis of nanomicelles with the size range of about 160 to 170 nm. The overall repressive effect of PTX@ANG/FA-NPs on human glioblastoma U251 cells was 1.2-times that of PTX alone. cellular uptake assay also demonstrated that the dual-targeted nanoparticles (NPs) were more easily taken up by glioblastoma U251 cells. Although the antiglioblastoma activity was confirmed by cell migration assay, apoptosis assay, and cellular uptake assay, the absorption was studied by fluorescence imaging and brain distribution. The synthesized PTX@ANG/FA-NPs probe significantly inhibited the migration of U251 within the cells and promoted the apoptosis process. Moreover, the RhB@ANG/FA-NPs and PTX@ANG/FA-NPs showed higher accumulating potential at sites of tumor BBB disruption. The novel nanodrug delivery system mediated enhanced distribution of drugs at the targeted site for therapeutics efficacies against glioblastomas across the BBB.
胶质母细胞瘤被认为是最致命的恶性脑肿瘤,起源于中枢神经系统(CNS),而血脑屏障(BBB)仍然是恶性脑肿瘤中药物主动靶向的最大挑战。因此,我们设计了一种紫杉醇PTX@ANG/FA-NPs新型纳米药物递送系统,它可以克服临床血脑屏障。PTX@ANG/FA-NPs的结构和形态表征证实成功合成了尺寸范围约为160至170nm的纳米胶束。PTX@ANG/FA-NPs对人胶质母细胞瘤U251细胞的总体抑制作用是单独紫杉醇的1.2倍。细胞摄取试验还表明,双靶向纳米颗粒(NPs)更容易被胶质母细胞瘤U251细胞摄取。尽管通过细胞迁移试验、凋亡试验和细胞摄取试验证实了抗胶质母细胞瘤活性,但通过荧光成像和脑分布研究了吸收情况。合成的PTX@ANG/FA-NPs探针显著抑制U251在细胞内的迁移并促进凋亡过程。此外,RhB@ANG/FA-NPs和PTX@ANG/FA-NPs在肿瘤血脑屏障破坏部位显示出更高的积累潜力。这种新型纳米药物递送系统介导药物在靶向部位的增强分布,以实现对跨越血脑屏障的胶质母细胞瘤的治疗效果。