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<p>Over-expression of transmembrane serine protease 4 (TMPRSS4), which promotes epithelial-to-mesenchymal transition and cancer cell invasion, is associated with poor prognosis in patients with gastric cancer. This study aimed to develop a new anti-TMPRSS4 small interfering RNA (siRNA) therapeutic strategy by engineering lipid nanoparticles (LNPs). The biodistribution and anti-tumor effect of anti-TMPRSS4-siRNA loaded LNPs were evaluated in vitro and in vivo in mice with gastric cancer tumors (subcutaneous xenograft NUGC-3 cell tumors). LNPs demonstrated enhanced accumulation in the tumor compared with naked siRNA. A significant reduction in gastric cancer tumor growth was observed in mice undergoing combination therapy with LNPs and fluorouracil (5-FU) compared to mice receiving 5-FU alone. Anti-TMPRSS4-siRNA loaded LNPs may be considered a promising therapeutic modality for gastric cancer.</p>

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Delivery of lipid nanoparticles containing small interfering RNA targeting transmembrane serine protease 4 in a human gastric cancer model using nude mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Hirofumi Tazawa,
  • Yuko Ishida,
  • Takahisa Suzuki,
  • Yosuke Shimizu,
  • Hirotaka Tashiro

摘要

Over-expression of transmembrane serine protease 4 (TMPRSS4), which promotes epithelial-to-mesenchymal transition and cancer cell invasion, is associated with poor prognosis in patients with gastric cancer. This study aimed to develop a new anti-TMPRSS4 small interfering RNA (siRNA) therapeutic strategy by engineering lipid nanoparticles (LNPs). The biodistribution and anti-tumor effect of anti-TMPRSS4-siRNA loaded LNPs were evaluated in vitro and in vivo in mice with gastric cancer tumors (subcutaneous xenograft NUGC-3 cell tumors). LNPs demonstrated enhanced accumulation in the tumor compared with naked siRNA. A significant reduction in gastric cancer tumor growth was observed in mice undergoing combination therapy with LNPs and fluorouracil (5-FU) compared to mice receiving 5-FU alone. Anti-TMPRSS4-siRNA loaded LNPs may be considered a promising therapeutic modality for gastric cancer.