(622ac) Delivery of Chemotherapeutic Drugs to Sensitize TRAIL Activity Against Gioblastoma Multiforme (GBM) Cells By Targeted MMP-Sensitive Peg-Hydrogel Microparticles

Authors: 
Erkoc, P., Koc University
Kizilel, S., Koc University
Bal, T., Koc University

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.