Tumour-specific delivery of ω-conotoxin MVIIA via engineered Salmonella for safe anticancer therapy

Solid tumours present a significant treatment challenge owing to the poor penetration of therapeutics into the tumour core. Bacteria offer a unique solution to this problem because they can selectively target tumours and proliferate within the tumour microenvironment.

In this study, we engineered Salmonella typhimurium to deliver MVIIA, a ω-conotoxin that inhibits N-type calcium channels. The engineered Salmonella strain was designed to efficiently secrete MVIIA via the flagellar type III secretion system (T3SS) under inducible control, ensuring tumour-specific delivery.

MVIIA-secreting Salmonella significantly inhibited the proliferation of human and mouse colon cancer cell lines in vitro, with similar effects observed in other solid tumour models. Engineered bacteria selectively localise to tumour tissues in vivo, persist within the tumour microenvironment, and are rapidly cleared from non-tumour organs. In vivo delivery of MVIIA-secreting Salmonella in a colon cancer model effectively suppressed tumor cell growth, improved survival, reduced the expression of proliferation markers, and increased the expression of apoptosis markers. Consistent antitumor effects were also observed in breast cancer and melanoma models. Notably, no systemic toxicity was detected, indicating the safety of this approach.

These findings demonstrate the potential of MVIIA-secreting Salmonella spp. as a novel drug delivery platform to address the key limitations of conventional therapies. This strategy provides a foundation for advancing bacterial-mediated treatments in oncology, with broad applicability to various solid tumours and the potential for integration into combination therapies.