title: Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging.
abstract: A multifunctional pH-sensitive superparamagnetic iron-oxide (SPIO) nanocomposite system was developed for simultaneous tumor magnetic resonance imaging (MRI) and therapy. Small-size SPIO nanoparticles were chemically bonded with antitumor drug doxorubicin (DOX) and biocompatible poly(ethylene glycol) (PEG) through pH-sensitive acylhydrazone linkages, resulting in the formation of SPIO nanocomposites with magnetic targeting and pH-sensitive properties. These DOX-conjugated SPIO nanocomposites exhibited not only good stability in aqueous solution but also high saturation magnetizations. Under an acidic environment, the DOX was quickly released from the SPIO nanocomposites due to the cleavage of pH-sensitive acylhydrazone linkages. With the help of magnetic field, the DOX-conjugated SPIO nanocomposites showed high cellular uptake, indicating their magnetic targeting property. Comparing to free DOX, the DOX-conjugated SPIO nanocomposites showed better antitumor effect under magnetic field. At the same time, the relaxivity value of these SPIO nanocomposites was higher than 146s(-1)mM(-1) Fe, leading to ~4 times enhancement compared to that of free SPIO nanoparticles. As a negative contrast agent, these SPIO nanocomposites illustrated high resolution in MRI diagnosis of tumor-bearing mice. All of these results confirm that these pH-sensitive SPIO nanocomposites are promising hybrid materials for synergistic MRI diagnosis and tumor therapy.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People's Republic of China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jianqi
authors.initials: J
authors.lastname: Li
authors.forename: Chunlai
authors.initials: C
authors.lastname: Tu
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.forename: Jieli
authors.initials: J
authors.lastname: Wu
authors.forename: Bangshang
authors.initials: B
authors.lastname: Zhu
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D003287:Contrast Media / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053761:Nanocomposites / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D003692:Delayed-Action Preparations; D058185:Magnetite Nanoparticles; D004317:Doxorubicin