Macrophage–Cancer Hybrid Membrane-Camouflaged Nanoplatforms for HIF-1α Gene Silencing-Enhanced Sonodynamic Therapy of Glioblastoma
Yunxia Li, Ying Liu, Jiaqing Xu, Dandan Chen, Tingting Wu, Yu Cao
Abstract
Fabrication of ingenious nanomedicines to penetrate the blood–brain barrier (BBB) and blood–brain–tumor barrier (BBTB) for efficient glioblastoma (GBM) therapy remains a big challenge. In this work, macrophage–cancer hybrid membrane-camouflaged nanoplatforms were fabricated for target gene silencing-enhanced sonodynamic therapy (SDT) of GBM. The J774.A.1 macrophage cell membrane and the U87 glioblastoma cell membrane were fused to create a hybrid biomembrane (JUM) with good BBB penetration and glioblastoma targeting capability for camouflaging. The ZIF-8 nanoparticles were synthesized for indocyanine green (ICG) and HIF-1α siRNA encapsulation (ICG-siRNA@ZIF-8, ISZ) with a high loading efficiency. After accumulation in the tumor sites, the pH sensitivity of the nanoplatform enabled release of ICG and HIF-1α siRNA in the tumor cells. Then, the expression of HIF-1α could be efficiently inhibited by the released HIF-1α siRNA to increase the SDT efficiency under hypoxic conditions. In vitro and in vivo experiments revealed that ISZ@JUM showed good BBB penetration and brain tumor-targeting capability and could achieve effective gene silencing-enhanced SDT, demonstrating great promise for clinical applications.