Delivery of a TNF-α–derived peptide by nanoparticles enhances its antitumor activity by inducing cell-cycle arrest and caspase-dependent apoptosis

摘要: Prostate cancer is the second-most common malignancy of male genitourinary system. TNF-α has attracted intense attention as a potential therapeutic agent against various cancers. However, its application restricted by short half life and severe toxic side-effects. In this study, we constructed stable nanodrug, called TNF-α-derived polypeptide (P16)-conjugated, chitosan (CTS)-modified selenium nanoparticle (SC; SCP), which composed SC slow-release carrier conjugated to P16. SCP had significant inhibitory effects on multiple types tumor cells, especially DU145 prostate but not RWPE-1 normal human epithelial cells. could induce G0/G1 cell-cycle arrest apoptosis in cells more effectively than P16 TNF-α. xenograft models, exerted much stronger antitumor or estramustine (the clinical drug for cancer) caused fewer addition, significantly inhibited proliferation accelerated tumors. Further mechanistic studies revealed that via activation p38 MAPK/JNK pathway, thus inducing caspase-dependent apoptosis. These findings suggest may represent long-lasting with side effects.-Yan, Q., Chen, X., Gong, H., Qiu, P., Xiao, Dang, S., Hong, A., Ma, Y. Delivery peptide nanoparticles enhances activity