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A novel anti-VEGF targeting and MRI-visible smart drug delivery system for specific diagnosis and therapy of liver cancer.
|Title||A novel anti-VEGF targeting and MRI-visible smart drug delivery system for specific diagnosis and therapy of liver cancer.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Huang H, Li Y, Li C, Wang Y, Sun Y, Wang J|
|Date Published||2013 Oct|
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.
|Alternate Journal||Macromol Biosci|