초록 |
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of cancer cells. However, TRAIL treatments are limited by its short half-life and poor in vivo stability. Therefore, we designed a TRAIL-loaded coacervate (Coa) embedded hydrogel platform, which can effectively localize and improve stability of TRAIL. Herein, we used (1) Coa consisting of mPEGylated poly(ethylene argininylaspartate diglyceride) and heparin for exogenous TRAIL delivery and (2) thiolated gelatin/poly(ethylene glycol) diacrylate composite hydrogels for an injectable reservoir. The release profile of TRAIL could be regulated by a two-step diffusional mechanism. Coa-mediated TRAIL delivery exhibited a higher cytotoxicity and apoptosis of colon cancers as compared with bolus TRAIL treatment. Consequently, TRAIL delivery system using Coa-embedded hydrogel could effectively maintain bioactivity of cargo proteins and control therapeutic dose in the tumor microenvironment. |