432000 Delivery of Chemotherapeutic Drugs to Sensitize TRAIL Activity Against Gioblastoma Multiforme (GBM) Cells By Targeted MMP-Sensitive Peg-Hydrogel Microparticles

Wednesday, November 11, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Pelin Erkoc1, Seda Kizilel2, Tugba Bagci Onder3, Ahmet Cingoz4 and Tugba Bal2, (1)Biomedical Sciences and Engineering, Koc University, Istanbul, Turkey, (2)Chemical and Biological Engineering, Koc University, Istanbul, Turkey, (3)School of Medicine, Koc University, Istanbul, Turkey, (4)Biomedical Sciences and Engineering, Koç University, Istanbul, Turkey

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.

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