Novel dual targeting cubosomes modified with angiopep-2 for co-delivery GNA and PLHSpT to brain glioma

作者：Lin, Tongyuan; Wei, Qing; Zhang, Huamin; Yang, Yong; Jiang, Bo; Wang, Zhangyi; Li, Siyuan; Wang, Qiang; Hu, Mengru; Chen, Weidong^*; Wang, Lei^*; Ding, Baijing^*

来源：JOURNAL OF BIOMATERIALS APPLICATIONS, 2024, 38(6): 743-757.

DOI：10.1177/08853282231217753

• Glioblastoma
• brain-targeting
• angiopep-2
• blood-brain barrier penetration
• cubosomes

3Glioblastoma multiforme is the most aggressive malignant brain tumor. However, the treatment of glioblastoma multiforme faces great challenges owing to difficult penetration of the blood-brain barrier. Therefore, more effective treatment strategies are desired quite urgently. In our study, a dual-targeting drug delivery system for co-loading with hydrophobic Gambogenic acid and hydrophilic PLHSpT was developed by cubosomes with angiopep-2 decorating. The Ang-cubs-(GNA + PLHSpT) was prepared by high-temperature emulsification-low-temperature solidification demonstrating excellent physical properties.Transmission electron microscopy revealed that Ang-cubs-(GNA + PLHSpT) was nearly spherical with a "core-shell" double-layer structure. Differential scanning calorimetry suggested that a new phase was formed. Small-angle X-ray scattering also verified that Ang-cubs-(GNA + PLHSpT) retains the Pn3m cubic. Moreover, laser confocal indicated that Ang-cubs-(GNA + PLHSpT) was capable of crossing BBB via binding to lipoprotein receptor-related protein-1, likely suggesting the potential tumor-specific targeting characteristic. Compared to free drug and cubs-(GNA + PLHSpT), Ang-cubs-(GNA + PLHSpT) was easily taken up by C6 cell and exhibited better anti-glioma effects in vitro. Importantly, GNA and PLHSpT co-loaded Ang-cubs could suppress tumor growth and significantly prolong survival in vivo. In conclusion, Ang-cubs-(GNA + PLHSpT) acts as a new dual-targeting drug delivery system for the treatment of GBM. @@@ Graphical Abstract

• 单位
  1; 哈尔滨医科大学