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

doi:10.1016/j.celrep.2022.111955

Cell-specific cargo delivery using synthetic bacterial spores

Cell Rep. 2023 Jan 31;42(1):111955. doi: 10.1016/j.celrep.2022.111955. Epub 2023 Jan 4.

Affiliations

¹ 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.
² Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
³ Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ Laboratory Animal Sciences Program, Leidos Biomedical Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: kandice.tanner@nih.gov.
⁷ Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: fitzgerd@mail.nih.gov.
⁸ Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ramamurthiks@mail.nih.gov.

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.

Keywords: Bacillus subtilis; CP: Cancer; Doxil; SpoIVA; SpoVM; drug delivery; microparticle; nanoparticle; spore; sporulation; synthetic biology.

Published by Elsevier Inc.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacillus subtilis / metabolism
Bacterial Proteins / metabolism
Cell Membrane / metabolism
Drug Delivery Systems
Humans
Mice
Neoplasms* / metabolism
Spores, Bacterial* / metabolism

Substances

Bacterial Proteins

Grants and funding

Z99 CA999999/ImNIH/Intramural NIH HHS/United States