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<p>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 <i>Buthus martensii Karsch (BmK</i> 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 <i>BmK</i> AGAP to improve its anti-tumor effectiveness. We engineered <i>E. coli</i> K12 to create the TSYPU strain, which not only expresses <i>BmK</i> 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 <i>BmK</i> 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年6月3日

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  • Yang Zhang,
  • Xianglong Li,
  • Chuanjun Tian,
  • Chunyan Zhong,
  • Wenwen Li,
  • Xiaobing Shang,
  • Minghui Zhao,
  • Yongshan Zhao

摘要

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.