Targeted delivery of doxorubicin into tumor cells via MMP-sensitive PEG hydrogel-coated magnetic iron oxide nanoparticles (MIONPs)

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 122; pp. 674 - 683
• Main Authors: Nazli, Caner, Demirer, Gozde S., Yar, Yasemin, Acar, H. Yagci, Kizilel, Seda
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Cancer; Coating; Coating effects; Controlled release; Doxorubicin; Doxorubicin - administration & dosage; Drug Carriers; Drug delivery systems; Ferric Compounds - chemistry; HeLa Cells; Humans; Hydrogels; Integrin targeting; Magnetic iron oxide nanoparticles; Magnetics; Matrix Metalloproteinases - chemistry; Metal Nanoparticles; Microscopy, Electron, Scanning; Nanostructure; Neoplasms - metabolism; Polyethylene Glycols - chemistry; Protease responsive PEG hydrogel coating; Targeted nanocarrier; Tumors; Magnetic iron oxide nanoparticles; Protease responsive PEG hydrogel coating; Doxorubicin; Targeted nanocarrier; Controlled release; Integrin targeting
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2014.07.049

•MMP-sensitive and RGDS functional PEG hydrogel coating around MIONPs is developed.•Multifunctional coating induces targeted drug release into cancer cells.•Cancer cell viability was compromised within 2h via targeted drug release.•Drug loaded nanoparticles have minimum cytotoxic damage to healthy cells.•The approach will be useful for cancer cell diagnosis and targeted drug delivery. Targeting tumors with nano-scale delivery systems shows promise to improve the therapeutic effects of chemotherapeutic drugs. However, the limited specificity of current nano-scale systems for cancer tissues prevents realization of their full clinical potential. Here, we demonstrate an effective approach to creating as targeted nanocarriers for drug delivery: MIONPs coated with integrin-targeted and matrix-metalloproteinase (MMP)—sensitive PEG hydrogel scaffolds. The functional PEG hydrogel coating has been designed for active loading as well as triggered intra-cellular release of the cancer therapeutic agent doxorubicin (DOX). Our study demonstrated that coated nanocarriers could be taken into cancer cells 11 times more efficiently than uncoated ones. Furthermore, confocal laser scanning microscopy images revealed that these targeted nanocarriers could efficiently deliver and release DOX into the nuclei of HeLa cells within 2h. Coating MIONPs with multifunctional PEG hydrogel could be a promising alternative to existing vehicles for targeted delivery of DOX into tumor tissue.