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September 17, 2026ACS Infectious Diseases

Targeted Inhibition of Intracellular Coxiella burnetii by Overcoming the Vacuolar Barrier with Autologous Exosomal Doxycycline

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Authors

YZYuxin ZhangXCXiaoxiao ChenJLJinru Lin

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Overview

Preclinical study demonstrates targeted exosomal delivery of doxycycline clears intracellular Coxiella burnetii in mice, indicating a potent strategy against refractory vacuolar pathogens.

Key Points

  • To develop a macrophage-derived exosomal delivery nanoplatform for doxycycline that bypasses the acidic vacuolar barrier to inhibit intracellular Coxiella burnetii.
  • Encapsulated doxycycline into exosomes harvested from THP-1 cell-derived macrophages (DOX@tExo).
  • Evaluated exosome internalization, lysosomal and vacuolar co-localization, and intracellular bacterial inhibition in vitro.
  • Assessed in vivo therapeutic clearance and organ bacterial burdens in a murine model of pulmonary Coxiella burnetii infection.
  • DOX@tExo accumulated within Coxiella-containing vacuoles and lowered the minimal effective concentration for intracellular bacterial inhibition to 0.015 μg/mL, more than an order of magnitude lower than free doxycycline.
  • DOX@tExo treatment concurrently suppressed autophagic cargo delivery, demonstrated by decreased accumulation of p62.
  • DOX@tExo significantly reduced bacterial burdens across multiple organs in a murine pulmonary infection model.

Cite This Study

Zhang et al. (2026) studied this question.

synapsesocial.com/papers/6aabb7f75f706d05830e752ahttps://doi.org/10.1021/acsinfecdis.6c00459
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