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Brain-Targeting Metastatic Tumor Cell Membrane Cloaked Biomimetic Nanomedicines Mediate Potent Chemodynamic and RNAi Combinational Therapy of Glioblastoma

Taking advantage of the non-invasive and high response characteristics of chemodynamic therapy (CDT), a biomimetic nanomedicine was developed with metastatic melanoma cell membrane as shell, charge-converted citraconic anhydride grafted poly-lysine (PLL-CA) as middle layer and siRNA-complexed polyethyleneimine xanthate (PEX) as the core. The developed biomimetic nanomedicines can effectively penetrate BBB. Interestingly, PEX chelates the abundant copper ions in tumor cells, resulting in GSH depletion and producing •OH via Fenton-like reaction to kill tumor cells. Additionally, the gene silencing of anti-apoptotic protein Bcl-2 leads to the increase of ROS level, which induces the apoptosis cascade of GBM cells. Excellent therapeutic effect and prolonged survival were achieved in both subcutaneous melanoma and orthotopic GBM tumor models.


The research paper was published in Advanced Functional Materials 2022, 2209239 (IF=19.925). Ph.D. candidate Dongya Zhang is the first author, and Prof. Shi, Prof. Zheng and A/Prof. Zou are the co-corresponding authors.


Paper link: https://doi.org/10.1002/adfm.202209239

 

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