title: A novel anti-VEGF targeting and MRI-visible smart drug delivery system for specific diagnosis and therapy of liver cancer.
abstract: A pH-responsive anticancer drug polymer conjugate p(aspartate)-graft-p(ethylene glycol)-dodecylamine-hydrazone-(adriamycin-levulinic acid) is synthesized as a magnetic resonance imaging (MRI)-visible and pH-sensitive drug delivery system. Being pH-sensitive, the anticancer drug ADR are stable in the polymeric micelles at neutral pH, resembling the physiological environment, whereas they release rapidly in acidic endosomal/lysosomal compartments of tumor cells for cancer therapy with the acid-linker breaking. For the purporse of MR imaging, the hydrophobic superparamagnetic iron oxide nanoparticles are encapsulated inside the core of the micelles. In order to identify the specific liver cancer tumors more efficiently, anti-vascular endothelial growth factor (anti-VEGF) is modified to the micelles. The stability studies show that all the conjugate@IO have excellent solubility and stability in stimulate biological media, suggesting that they have longer circulation time. Drug release studies in vitro show that the ADR release from the pH-sensitive polymeric micelles is significantly faster at pH 5.0 than at of pH 7.4. The tetrazolium dye method (MTT assay) shows that all the conjugate@IO exhibit low cytotoxicity and high antitumor activities against HepG2 cells. Furthermore, the anti-VEGF-conjugate@IO shows a high spin-spin (T2) relaxivity. In vivo MRI experiments on tumor-bearing mice demonstrate that the anti-VEGF-conjugate@IO achieves an appreciable accumulation into liver tumor, suggesting their potential utility as tumor-selective MRI contrast agents.
authors.affiliation: Alan G. MacDiarmid Institute of Jilin University, Jilin University, Changchun 130012, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Huang
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.forename: Caijin
authors.initials: C
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008823:Micelles; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D008823:Micelles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide; D004317:Doxorubicin
keywords: MRI; antitumor; drug delivery; iron oxide NPs; pH-responsive