1. Enhancing glioma-specific drug delivery through self-assembly of macrophage membrane and targeted polymer assisted by low-frequency ultrasound irradiation
- Author
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Junqing Lin, Zhenhu Lin, Leilei Liu, Wenjin Lin, Xiaodong Xie, and Xiujuan Zhang
- Subjects
Glioma ,Bone marrow-derived macrophage membrane ,Targeted drug delivery ,Temozolomide ,Low-frequency ultrasound irradiation ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The blood-brain Barrier (BBB), combined with immune clearance, contributes to the low efficacy of drug delivery and suboptimal treatment outcomes in glioma. Here, we propose a novel approach that combines the self-assembly of mouse bone marrow-derived macrophage membrane with a targeted positive charge polymer (An-PEI), along with low-frequency ultrasound (LFU) irradiation, to achieve efficient and safe therapy for glioma. Our findings demonstrate the efficacy of a charge-induced self-assembly strategy, resulting in a stable co-delivery nanosystem with a high drug loading efficiency of 44.2 %. Moreover, this structure triggers a significant release of temozolomide in the acidic environment of the tumor microenvironment. Additionally, the macrophage membrane coating expresses Spyproteins, which increase the amount of An-BMP-TMZ that can evade the immune system by 40 %, while LFU irradiation treatment facilitates the opening of the BBB, allowing for enormously increased entry of An-BMP-TMZ (approximately 400 %) into the brain. Furthermore, after crossing the BBB, the Angiopep-2 peptide-modified An-BMP-TMZ exhibits the ability to selectively target glioma cells. These advantages result in an obvious tumor inhibition effect in animal experiments and significantly improve the survival of glioma-bearing mice. These results suggest that combining the macrophage membrane-coated drug delivery system with LFU irradiation offers a feasible approach for the accurate, efficient and safe treatment of brain disease.
- Published
- 2024
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