(783d) Stimuli Responsive Poly (ethylene glycol) (PEG) Hydrogel Coated Magnetic Iron Oxide Nanoparticles for Targeted Drug Delivery

One of the major limitations of nanoparticle-based cancer therapeutics is non-specific distribution of drugs in the body. Undesirable side effects and resistance of cancer cells to drugs are some of the additional limitations of a successful cancer therapy. Magnetic iron oxide nanoparticles (MIONPs) has demonstrated great potential for simultaneous imaging and targeted delivery of therapeutic agents into tumor site. The aim of this study was synthesis and characterization of enzymatically responsive poly (ethylene glycol) (PEG) hydrogel coated MIONPs for cancer cell targeted drug delivery. RGDS short peptide as a targeting ligand and GGGPQGIWGQGK peptide as matrix metalloprotease (MMP) responsive degradable peptide sequences were used for the design of functionalized PEG hydrogel coating. MIONPs could be internalized into cancer cells due to RGDS functionalized PEG hydrogel coating, and degradable sequence within PEG hydrogel structure allows for the accelerated release of therapeutic drugs into cytoplasm. Intracellular uptake studies via Prussian blue staining and inductively coupled plasma optical emission spectrometry with HeLa cells demonstrated that the protease responsive and RGDS-functionalized PEG hydrogel-coated MIONPs were superior compared to bare or only PEG hydrogel-coated MIONPs. In addition, in vitro release of doxorubicin from protease responsive PEG hydrogel coated nanoparticles was characterized, and viability of cancer cells exposed to this nanoparticle system has been studied. We find that both RGDS and protease responsive coating play a role in enhancing nanoparticle internalization into HeLa cells and lead to reduced cancer cell viability. This approach may be beneficial for enhanced cancer drug efficiency and for reduced the systemic side effects of loaded drugs.