Macrophage–Cancer Hybrid Membrane-Camouflaged Nanoplatforms for HIF-1α Gene Silencing-Enhanced Sonodynamic Therapy of Glioblastoma

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.

Metal-organic framework-mediated siRNA delivery and sonodynamic therapy for precisely triggering ferroptosis and augmenting ICD in osteosarcoma

“…This is also supported by the results of colony formation experiments. Improving chemotherapy resistance is likely related to the large amount of ROS induced intracellularly by synergistic treatment [ 14 ]. In addition, inactivation of GPX4 may also lead to enhanced sensitivity of 143B–R cells to CDDP [ 57 , 58 ].…”

“…By combining the synergetic effects of an acoustic sensitizer, US, and oxygen (O 2 ), SDT selectively kills tumor cells by producing a lethal dose of ROS [ 13 ]. Recent evidence indicates that synergistic therapy with SDT and RNAi has promising therapeutic effects on tumors [ 14 ]. Nevertheless, certain conditions, such as hypoxia and high GSH in the solid tumor TME, can limit the therapeutic efficacy of SDT [ 15 ].…”

Recent advances in sonodynamic therapy strategies for pancreatic cancer

“…As pancreatic cancer is a malignant deep‐seated tumor, several emerging phototherapy methods face certain limitations in terms of treatment depth. SDT, which combines low‐frequency sound waves with specific chemical drugs, can overcome these limitations owing to its ability to penetrate into deeper tumor tissues (Y. Li, Liu, et al, 2023; Xiao et al, 2023; Zhu, Luo, et al, 2023). The frequency and intensity of sound waves can be adjusted according to the depth of cancer cells, ensuring that drugs and sound waves can penetrate through the surrounding stroma and exert their effects in deeper locations.…”

Biomimetic Dual-Target Theranostic Nanovaccine Enables Magnetic Resonance Imaging and Chemo/Chemodynamic/Immune Therapy of Glioma

“…Even for postparenteral administration, there are still approximately 98% of small molecules and 99.9% of biomolecules that are prevented from entering the brain through the BBB . Therefore, urgent strides are required to develop BBB-crossing advanced drug delivery systems to effectively combat glioma and impede its recurrence …”