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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.
Tazawa et al. (Mon,) studied this question.