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Updated: Aug 14, 2025
Directed Protein Packaging within Outer Membrane Vesicles from Escherichia coli: Design, Production and Purification
Published on: November 16, 2016
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.
Abstract:
Delivery of cancer therapeutics to non-specific sites decreases treatment efficacy while increasing toxicity. In ovarian cancer, overexpression of the cell surface marker HER2, which several therapeutics target, relates to poor prognosis. We recently reported the assembly of biocompatible bacterial spore-like particles, termed "SSHELs." Here, we modify SSHELs with an affibody directed against HER2 and load them with the chemotherapeutic agent doxorubicin. Drug-loaded SSHELs reduce tumor growth and increase survival with lower toxicity in a mouse tumor xenograft model compared with free drug and with liposomal doxorubicin by preferentially accumulating in the tumor mass. Target cells actively internalize and then traffic bound SSHELs to acidic compartments, whereupon the cargo is released to the cytosol in a pH-dependent manner. We propose that SSHELs represent a versatile strategy for targeted drug delivery, especially in cancer settings.
Insights
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.
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.
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