Engineered Bacteria-Mediated Delivery of Scorpion Venom Peptide AGAP for Targeted Breast Cancer Therapy

The rising incidence and mortality rates of malignant tumors highlight their profound impact on human health. Bacterial therapy has emerged as a promising avenue in oncological research. Our lab has isolated an analgesic-anti-tumor peptide from the venom of Buthus martensii Karsch (BmK AGAP), a long-chain scorpion venom peptide, which exhibits remarkable anti-tumor activity. However, the limited bioavailability of peptides poses a challenge for their therapeutic efficacy. To address this challenge, we focused on enhancing the delivery of BmK AGAP to improve its anti-tumor effectiveness. We engineered E. coli K12 to create the TSYPU strain, which not only expresses BmK AGAP, but also possesses lytic capabilities. Co-culturing of TSYPU with murine breast cancer 4T1 cells in vitro demonstrated its potential as a drug delivery platform. Further advancements included the encapsulation of TSYPU with nanogold particles, resulting in TSYPU@Au strain. In vivo experiments revealed that TSYPU@Au exhibited a significant anti-tumor effect, crucially overcoming degradation in the acidic gastrointestinal environment. In summary, our study highlights the viability of engineered TSYPU bacteria as carriers for BmK AGAP delivery, offering a promising approach for the rational design of bacterial-based peptide drug delivery systems in oncology. This strategy has considerable potential for advancing the field and warrants further investigation in future studies.