<p>Tumor-derived extracellular vesicles (TEVs) are promising autologous cancer vaccines due to their intrinsic tumor-associated antigens. However, their translation is hindered by immune evasion and the lack of non-invasive tools to monitor vaccination efficacy in vivo. Here, we report a self-reporting nanovaccine engineered by coating TEVs under microfluidics with pH-sensitive manganese dioxide (mTEV). This surface biomineralization on TEVs chemically block inhibitory ligands such as CD47, promoting dendritic cell (DC) uptake and degrades under lysosomal conditions to expose tumor antigens and release Mn<sup>2+</sup>. The released Mn<sup>2+</sup> activates the cGAS-STING pathway and simultaneously enhances T<sub>1</sub>-weighted magnetic resonance imaging (MRI) contrast, enabling visualization of DC trafficking. In ovarian cancer models, mTEVs drove robust DC maturation, antigen presentation, and cytotoxic T cell responses, effectively suppressing tumor growth and peritoneal dissemination. Importantly, early MRI signals in draining lymph nodes correlated with treatment outcomes, providing a non-invasive predictive biomarker of vaccine efficacy. This dual-functional nanovaccine platform integrates immune activation with in vivo tracking, offering a precision strategy for cancer immunotherapy.</p> Graphical Abstract <p></p>

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Microfluidics engineered autologous nanovaccine for activating and visualizing antitumor activity

  • Xiaoting Jiang,
  • Jiacheng Song,
  • Yunfei Mu,
  • Guangyue Zu,
  • Ruiheng Wang,
  • Xisheng Liu,
  • Xianguang Ding,
  • Ting Chen

摘要

Tumor-derived extracellular vesicles (TEVs) are promising autologous cancer vaccines due to their intrinsic tumor-associated antigens. However, their translation is hindered by immune evasion and the lack of non-invasive tools to monitor vaccination efficacy in vivo. Here, we report a self-reporting nanovaccine engineered by coating TEVs under microfluidics with pH-sensitive manganese dioxide (mTEV). This surface biomineralization on TEVs chemically block inhibitory ligands such as CD47, promoting dendritic cell (DC) uptake and degrades under lysosomal conditions to expose tumor antigens and release Mn2+. The released Mn2+ activates the cGAS-STING pathway and simultaneously enhances T1-weighted magnetic resonance imaging (MRI) contrast, enabling visualization of DC trafficking. In ovarian cancer models, mTEVs drove robust DC maturation, antigen presentation, and cytotoxic T cell responses, effectively suppressing tumor growth and peritoneal dissemination. Importantly, early MRI signals in draining lymph nodes correlated with treatment outcomes, providing a non-invasive predictive biomarker of vaccine efficacy. This dual-functional nanovaccine platform integrates immune activation with in vivo tracking, offering a precision strategy for cancer immunotherapy.

Graphical Abstract