Engineered Bacterial Outer Membrane Vesicles‐Based Doxorubicin and CD47‐siRNA Co‐Delivery Nanoplatform Overcomes Immune Resistance to Potentiate the Immunotherapy of Glioblastoma

• DOI: 10.1002/adma.202418053
• Publication Date: 2025-03-11T21:54:58Z
• Authors: Haoyu You; Shilin Zhang; Yiwen Zhang; Qinjun Chen; Yuxing Wu; Zheng Zhou; Zhenhao Zhao; Boyu Su; Xuwen Li; Yun Guo; Yun Chen; Weiyi Tang; Bing Liu; Hongrui Fan; Shuo Geng; Mingzhu Fang; Fangxin Li; Guangna Liu; Chen Jiang; Tao Sun
• Keywords: CD47

Abstract Apart from the blood‐brain barrier (BBB), efficacy of immunotherapy for glioblastoma (GBM) is limited by presence intrinsic and adaptive immune resistance, implying that co‐delivery various immunotherapeutic agents or simultaneous regulation different cells urgently needed. Bacterial outer membrane vesicles (OMVs) offer a unique advantage in treatment GBM, owing to their multifunctional properties as carriers adjuvants ability cross BBB. However, traditional OMVs can lead toxic side effects disruption tight junctions Therefore, enhance vivo safety targeting capability OMVs, we introduced engineered reduce toxicity further constructed modularly assembled nanoplatform performing simple peptide modifications. This demonstrates satisfactory biosafety able continuously BBB target GBM with assistance Angiopep‐2. Subsequently, immunogenic substances on along carried small‐interfering RNA (siRNA) doxorubicin, promote reprogramming phagocytic abilities macrophages microglia, respectively, increase immunogenicity ultimately overcoming resistance immunotherapy. OMVs‐based provides new paradigm insights into development GBM.