Delivery of chemotherapeutic drugs to sensitize TRAIL activity against Gioblastoma Multiforme (GBM) cells by targeted MMP-sensitive PEG-Hydrogel Microparticles
Targeting cancer cell surfaces and microenvironment via micro- and nano-range delivery vehicles is a promising approach for the treatment of cancer. These delivery vehicles improve the efficacy of chemotherapeutic drugs through functionalization and controlled release properties of delivery systems. TNFα-related apoptosis-inducing ligand (TRAIL) has been recently investigated as a therapeutic protein that induces cell death in human, particularly in cancer cells. Despite its success, some malignant cancer cell types can develop resistance to TRAIL-induced apoptosis. As a result, drug repositioning becomes more important to sensitize cancer cells to TRAIL- induced apoptosis.
In this study, we used integrin-targeting ligand functionalized and matrix-metalloproteinase (MMP)-sensitive poly (ethylene glycol) (PEG) hydrogels to synthesize microgels via water-in-water emulsion technique. Emulsions were prepared in dextran, where visible-light-induced photolymerization was used for microgel synthesis. The physicochemical properties of microgels were characterized via Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM).
The widely used FDA-approved drug, 03TR4, was used in combination with TRAIL. 03TR4 was encapsulated with PEG microgels and evaluated for its ability to sensitize GBM cells to TRAIL-induced apoptosis. Our results showed that cytotoxic potency of TRAIL could be improved with 03TR4, which suggests a cooperation between the drug and TRAIL. This study is the first report about the delivery of 03TR4 drug from a biocompatible system for effective treatment of cancer cells.
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division