Peritoneal Gene Transfection of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand for Tumor Surveillance and Prophylaxis

Peritoneal metastasis is very common in gastrointestinal,reproductive,and genitourinary tract cancers in late stages or postsurgery, causingpoor prognosis, so effective and nontoxic prophylactic strategiesagainst peritoneal metastasis are highly imperative. Herein, we demonstratethe first gene transfection as a nontoxic prophylaxis preventing peritonealmetastasis or operative metastatic dissemination. Lipopolyplexes ofTNF-related-apoptosis-inducing-ligand (TRAIL) transfected peritoneaand macrophages to express TRAIL for over 15 days. The expressed TRAILselectively induced tumor cell apoptosis while exempting normal tissue,providing long-term tumor surveillance. Therefore, tumor cells inoculatedin the pretransfected peritoneal cavity quickly underwent apoptosisand, thus, barely formed tumor nodules, significantly prolonging themouse survival time compared with chemotherapy prophylaxis. Furthermore,lipopolyplex transfection showed no sign of toxicity. Therefore, thisperitoneal TRAIL-transfection is an effective and safe prophylaxis,preventing peritoneal metastasis.

Automated summary

Peritoneal metastasis is common in late-stage or postsurgery gastrointestinal, reproductive, and genitourinary tract cancers, leading to poor prognosis. Therefore, finding effective and nontoxic prophylactic strategies against peritoneal metastasis is crucial. This study demonstrates the first gene transfection as a nontoxic prophylaxis for preventing peritoneal metastasis or operative metastatic dissemination. TRAIL-transfected lipopolyplexes enable long-term expression of TRAIL in the peritoneum and macrophages, selectively inducing tumor cell apoptosis while sparing normal tissue, effectively preventing tumor nodules formation and prolonging mouse survival time compared to chemotherapy prophylaxis.