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<p>Developing multifunctional nanoplatforms capable of addressing the excessive oxidative stress and cytokine storm in inflammatory diseases remains a challenging task. Herein, we report the construction of stimuli-responsive nanogels (NGs) through a reverse microemulsion method utilizing taxifolin (Tax)-functionalized generation 3 poly(amidoamine) dendrimers as a monomer and diselenide compound as a crosslinker. Subsequently, exosomes derived from mesenchymal stem cells (MSC-Exos) were coated on the surface of the NGs. The formed multifunctional biomimetic NGs (MSC@DT-NGs) with an average size of 78.3 nm exhibit good colloidal stability and hydrogen peroxide/pH-dual responsive drug release behavior. Meanwhile, the MSC-Exo coating affords the NGs with excellent macrophage targeting ability to enter the target cells via the clathrin-mediated endocytosis pathway, effectively alleviating intracellular excessive oxidative stress and balancing the antioxidant system through the incorporated anti-oxidant Tax. Furthermore, the MSC@DT-NGs polarize activated macrophages towards the anti-inflammatory M2 phenotype and quell the cytokine storm by inhibiting the intracellular nuclear factor-kappa B signaling pathway. Notably, the MSC@DT-NGs effectively repair lung injury and alleviate acute lung injury (ALI) symptoms by controlling pulmonary inflammation, reducing oxidative stress levels, as well as inhibiting neutrophil infiltration as demonstrated by an ALI mouse model. This study presents an innovative dual-responsive biomimetic nanoplatform that integrates Tax and MSC-Exos for targeted antioxidant delivery and immunomodulation, providing a translational strategy for treating inflammatory disorders.</p>

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Exosome-coated responsive dendrimer nanogels enable combined immunomodulation and antioxidant treatment of acute lung injury

  • 期刊论文

  • 发表日期：

    2025年7月24日

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  • Jingjing Li,
  • Huxiao Sun,
  • Yanying Li,
  • Yifan Huang,
  • Jiajia Liang,
  • Zhiyun Liu,
  • Mingwu Shen,
  • Xiangyang Shi

摘要

Developing multifunctional nanoplatforms capable of addressing the excessive oxidative stress and cytokine storm in inflammatory diseases remains a challenging task. Herein, we report the construction of stimuli-responsive nanogels (NGs) through a reverse microemulsion method utilizing taxifolin (Tax)-functionalized generation 3 poly(amidoamine) dendrimers as a monomer and diselenide compound as a crosslinker. Subsequently, exosomes derived from mesenchymal stem cells (MSC-Exos) were coated on the surface of the NGs. The formed multifunctional biomimetic NGs (MSC@DT-NGs) with an average size of 78.3 nm exhibit good colloidal stability and hydrogen peroxide/pH-dual responsive drug release behavior. Meanwhile, the MSC-Exo coating affords the NGs with excellent macrophage targeting ability to enter the target cells via the clathrin-mediated endocytosis pathway, effectively alleviating intracellular excessive oxidative stress and balancing the antioxidant system through the incorporated anti-oxidant Tax. Furthermore, the MSC@DT-NGs polarize activated macrophages towards the anti-inflammatory M2 phenotype and quell the cytokine storm by inhibiting the intracellular nuclear factor-kappa B signaling pathway. Notably, the MSC@DT-NGs effectively repair lung injury and alleviate acute lung injury (ALI) symptoms by controlling pulmonary inflammation, reducing oxidative stress levels, as well as inhibiting neutrophil infiltration as demonstrated by an ALI mouse model. This study presents an innovative dual-responsive biomimetic nanoplatform that integrates Tax and MSC-Exos for targeted antioxidant delivery and immunomodulation, providing a translational strategy for treating inflammatory disorders.