Systemic administration of anticancer drugs can cause indiscriminate drug distribution and severe toxic side effects. To reduce these shortcomings, targeted drug delivery systems have been considered an attractive option for cancer therapy. Here we developed a novel drug delivery system using synthetic bacterial spore-like particles that our lab recently developed. These particles, termed “SSHELs”, consist of 1 µm-diameter mesoporous silica beads covered in a lipid bilayer, and encased by two spore coat proteins from the bacterium Bacillus subtilis that tether to the lipid bilayer and polymerize to form a stable shell around the silica bead. The proteinaceous surface of these particles were covalently decorated with ~88,000 copies/particle of affibodies directed towards human epidermal growth factor receptor 2 (HER2), which is overproduced in ~25% of diagnosed breast cancers. SSHELs displaying anti-HER2 affibodies (SSHELαHER2) displayed specific binding to HER2-overproducing breast and ovarian cancer cells. Next, we demonstrated that the porous interior of SSHELs can be loaded with ~107 molecules/particle of the chemotherapeutic drug doxorubicin (DOX). SSHELαHER2 particles loaded with DOX effectively and specifically induced apoptosis and reduced the viability of HER2-positive cancer cells. Confocal microscopy showed that internalized SSHELsαHER2 were trafficked to acidic organelles, and an in vitro drug release assay revealed that acidic conditions (pH 5.0) triggered rapid release of encapsulated DOX from SSHELs. Taken together, we propose that SSHELs can be modified to target specific cell types and, once internalized into an acidic compartment, can release and deliver encased cargo to the target cell. Ongoing experiments in animal models are currently testing the efficacy of SSHELs as vehicles for targeted drug delivery to tumors in vivo.

Targeted drug delivery to cancer cells using synthetic bacteria

256th National Meeting (2018)

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