title: Targeted delivery of doxorubicin into tumor cells via MMP-sensitive PEG hydrogel-coated magnetic iron oxide nanoparticles (MIONPs).
abstract: 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.
authors.affiliation: Koç University, Material Science and Engineering, Istanbul 34450, Turkey.
authors.forename: Caner
authors.initials: C
authors.lastname: Nazli
authors.affiliation: Koç University, Chemical and Biological Engineering, Istanbul 34450, Turkey.
authors.forename: Gozde S
authors.initials: GS
authors.lastname: Demirer
authors.affiliation: Koç University, Material Science and Engineering, Istanbul 34450, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Yar
authors.affiliation: Koç University, Material Science and Engineering, Istanbul 34450, Turkey; Koç University, Chemistry Department, Istanbul 34450, Turkey.
authors.forename: H Yagci
authors.initials: HY
authors.lastname: Acar
authors.affiliation: Koç University, Material Science and Engineering, Istanbul 34450, Turkey; Koç University, Chemical and Biological Engineering, Istanbul 34450, Turkey. Electronic address: skizilel@ku.edu.tr.
authors.forename: Seda
authors.initials: S
authors.lastname: Kizilel
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D005290:Ferric Compounds / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels; D008280:Magnetics; D020782:Matrix Metalloproteinases / Q000737:chemistry*; D053768:Metal Nanoparticles; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005290:Ferric Compounds; D020100:Hydrogels; C000499:ferric oxide; D011092:Polyethylene Glycols; D004317:Doxorubicin; D020782:Matrix Metalloproteinases
keywords: Controlled release; Doxorubicin; Integrin targeting; Magnetic iron oxide nanoparticles; Protease responsive PEG hydrogel coating; Targeted nanocarrier