title: Integrin-targeting thermally cross-linked superparamagnetic iron oxide nanoparticles for combined cancer imaging and drug delivery.
abstract: We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine-glycine-aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGD_TCL-SPION) had a mean hydrodynamic size of 34 ± 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGD_TCL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin α(v)β(3)+) when analyzed by T(2)-weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGD_TCL-SPION via ionic interaction, the resulting Dox-loaded cRGD_TCL-SPION (Dox@cRGD_TCL-SPION) showed much higher cytotoxicity in U87MG cells than Dox@TCL-SPION lacking cRGD (IC(50) value of 0.02 µM versus 0.12 µM). These results suggest that Dox@cRGD_TCL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Yu
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Jeong
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003952:Diagnostic Imaging / Q000379:methods*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D057446:Hydrodynamics; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D018613:Microscopy, Confocal; D010316:Particle Size; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D055767:Immobilized Proteins; D016023:Integrins; D058185:Magnetite Nanoparticles; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D004317:Doxorubicin