Engineered endothelial cells targeting and dihydrotanshinone I loaded bacterial extracellular vesicles for

Rong-Rong Zhu1, Xue-Liang Zhou2, Yan-Wei Liu1

  • 1Department of Cardiology The Affiliated Hospital of Jiangxi University of Chinese Medicine Nanchang China.

Insights

Engineered endothelial cell-targeted extracellular vesicles loaded with dihydrotanshinone I (DHT) show promise for treating atherosclerosis (AS). This novel therapy effectively reduced AS in mice, offering a potential alternative to traditional treatments.

Area of Science:

  • Cardiovascular Research
  • Nanomedicine
  • Cell Biology

Background:

  • Atherosclerosis (AS) is a complex cardiovascular disease involving endothelial dysfunction, dyslipidemia, and inflammation.
  • Current treatments like statins have limitations in efficacy and side effects.
  • Novel therapeutic strategies are needed to combat AS effectively.

Purpose of the Study:

  • To investigate the anti-atherosclerotic effects of engineered endothelial cell-targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (EC-BEVsDHT).
  • To explore the molecular mechanisms underlying the therapeutic potential of EC-BEVsDHT in AS treatment.
  • To evaluate the efficacy and safety of EC-BEVsDHT as a novel therapeutic strategy for AS.

Main Methods:

  • Characterization of EC-BEVsDHT using transmission electron microscopy and nanoparticle tracking analysis.
  • Confirmation of ECs-targeting peptide VSSSTPR expression via HPLC-MS/MS.
  • In vitro assessment of EC-BEVsDHT effects on oxidized LDL-induced HUVECs injury.
  • In vivo evaluation of EC-BEVsDHT in Apolipoprotein E-deficient (ApoE-/-) mice models of AS.

Main Results:

  • EC-BEVsDHT exhibited spherical morphology and appropriate particle size.
  • The ECs-targeting peptide VSSSTPR was successfully incorporated into the vesicles.
  • EC-BEVsDHT significantly attenuated oxidized low-density lipoprotein-induced HUVECs injury in vitro.
  • EC-BEVsDHT demonstrated a significant decrease in atherosclerosis progression in ApoE-/- mice in vivo.

Conclusions:

  • Engineered endothelial cell-targeting probiotic extracellular vesicles loaded with dihydrotanshinone I (EC-BEVsDHT) represent a promising novel therapeutic approach for atherosclerosis.
  • This strategy effectively reduces AS in preclinical models, suggesting potential advantages over conventional treatments.
  • EC-BEVsDHT offer a potential new avenue for managing cardiovascular disease with improved safety and efficacy.

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