Cell-specific cargo delivery using synthetic bacterial spores
Minsuk Kong,
Domenico D’Atri,
Maria Teresa Bilotta,
Bailey Johnson,
Taylor B. Updegrove,
Devorah L. Gallardo,
Federico Machinandiarena,
I-Lin Wu,
Maira Alves Constantino,
Stephen M. Hewitt,
Kandice Tanner,
David J. Fitzgerald,
Kumaran S. Ramamurthi
Affiliations
Minsuk Kong
Laboratory 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
Domenico D’Atri
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Maria Teresa Bilotta
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Bailey Johnson
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Taylor B. Updegrove
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Devorah L. Gallardo
Laboratory Animal Sciences Program, Leidos Biomedical Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Federico Machinandiarena
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
I-Lin Wu
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Maira Alves Constantino
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Stephen M. Hewitt
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Kandice Tanner
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
David J. Fitzgerald
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Kumaran S. Ramamurthi
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Summary: 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.
