Unveiling the Cytotoxic Potential of Quercetin-Loaded Magnetic Bacterial Bots against Cervical Cancer

Bacterial bots are potent vehicles in cancer theranostics where bacteria are used typically as cargos for drug delivery. However, living bacteria themselves may aid in their efficiency in killing the tissues. For example, living bacteria may be functionalized with magnetic and luminescent nanoparticles along with drugs in order to achieve the targeted delivery and release of payloads that would include the bacteria. In this study, we elucidate the synergistic impact of human-friendly living <i>Lactobacillus rhamnosus</i> bacteria decorated with gold nanoclusters and quercetin-loaded magnetic nanoparticles against the HeLa-cervical cancer cells. The cytotoxicity of the fabricated magnetic bacterial bots within the low dose (5 × 10⁵ CFU/mL) against the HeLa monolayer and 3D spheroid model was found around 84%, which had remarkably enhanced up to more than 91% in the presence of an external magnet. The antiproliferative action of magnetic bacterial bots was demonstrated by the escalation of generated reactive oxygen species from 1.8- to 2.3-fold. Cells treated with magnetic bacterial bots showed a decrease in lipid droplet content, along with altered cell cycle patterns, which led to 74% (average population) of cells being exposed to necroptosis. The study highlights the cytotoxic potential of magnetic bacterial bots against cervical cancer cells outweighing that of the quercetin or the bacteria only, ensuring an external-magnetic-field-responsive targeted drug delivery system.