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Cell-specific cargo delivery using synthetic bacterial spores.

Minsuk Kong1, Domenico D'Atri2, Maria Teresa Bilotta2

  • 1Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Department of Food Science and Technology, Seoul National University of Science and Technology, Seoul 01811, South Korea.

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|January 14, 2023
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Engineered bacterial spore-like particles (SSHELs) target HER2-expressing ovarian cancer cells, delivering doxorubicin chemotherapy. This targeted approach reduces tumor growth and toxicity in mice, improving survival rates.

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Bacillus subtilisCP: CancerDoxilSpoIVASpoVMdrug deliverymicroparticlenanoparticlesporesporulationsynthetic biology

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Oncology

Background:

  • Targeted cancer therapy improves efficacy and reduces toxicity.
  • HER2 overexpression in ovarian cancer correlates with poor prognosis.
  • Bacterial spore-like shells (SSHELs) offer a novel drug delivery platform.

Purpose of the Study:

  • To develop HER2-targeted SSHELs for ovarian cancer treatment.
  • To evaluate the efficacy and toxicity of doxorubicin-loaded SSHELs.
  • To investigate the cellular uptake and drug release mechanism of SSHELs.

Main Methods:

  • SSHELs were modified with an anti-HER2 affibody.
  • Doxorubicin was loaded into the modified SSHELs.
  • Efficacy and toxicity were assessed in a mouse xenograft model.

Main Results:

  • SSHELs preferentially accumulated in tumor masses.
  • Drug-loaded SSHELs reduced tumor growth and increased survival.
  • Lower toxicity was observed compared to free drug and liposomal doxorubicin.
  • SSHELs were internalized by target cells and released doxorubicin in an acidic, pH-dependent manner.

Conclusions:

  • HER2-targeted SSHELs represent a promising strategy for ovarian cancer drug delivery.
  • This platform demonstrates enhanced therapeutic efficacy and reduced systemic toxicity.
  • SSHELs facilitate targeted internalization and pH-dependent drug release within cancer cells.