Anti-HER2 cell specific doxorubicin delivery using synthetic bacterial spores for resistant ovarian cancer treatment.

Abstract

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. SSHELs are synthetic spore-like particles wherein the spore’s cell surface is partially reconstituted around 1 μm-diameter silica beads. Via a unique cysteine engineered protein, the surface of SSHELs may be covalently decorated to display HER2 (SSHELs αHER2). SKOV3 and SKBR3 cells’ targeting by SSHELs αHER2was evaluated by flow cytometry and confocal microscopy. SSHELs αHER2specifically bound to target cells and were internalized proportionally to their concentration. Subsequently, SSHELs were successfully loaded with doxorubicin (Dox-SSHELs αHER2). Dox-SSHELs αHER2capabilities to kill tumor cells was evaluated by flow cytometry and caspase assay. HER2 negative cells were used as a control. Dox-SSHELs αHER2’s efficacy was tested in vivo using athymic nude mice injected with SKOV3 ovarian cancer cells and then treated for up to 40 days. Dox-SSHELs αHER2can reduce SKOV3 tumor growth up to 75% when compared to the free drug. Further, when compared to liposomal doxorubicin (Doxil TM) Dox-SSHELs αHER2showed similar efficacy in reducing tumor growth, but without any of the typical side effects correlated with Doxil TMinjections. With a facile, reproducible manufacturing process that allows for straightforward targeting towards specific cell types, and lower overall toxicity, we suggest that SSHELs may represent a versatile strategy opening new research avenues for targeted drug delivery treatment or immune system stimulation through vaccination.