Objective: To evaluate the biological efficacy of TBATP and their distribution in the inner ear after transtympanic injection. Methods: TBATP was synthesized through standard Fmoc solid phase synthesis. A model of TNF-α-induced apoptosis was established in human umbilical vein endothelial cells (HUVECs). The peptides were covalently attached onto CAN-γ-Fe2 O3 NPs. Nanoparticle suspension was injected to rat middle ear cavity. Distribution of CAN-γ-Fe2 O3 NPs in the inner ear was detected using a 7.0 T MRI machine in combination with Prussian blue staining. Results: TBATP almost fully suppressed the inhibitory effect on HUVECs induced by TNF-α while the linear one reduced less than half of the effect. CAN-γ-Fe2 O3 NPs conjugated to TBATP at a peptide weight ratio of 10% but not 50% efficiently entered the inner ear at 3 h through 2 w post-middle ear administrations and most pronounced at 2 w. Conclusion: The tetra-branched anti-TNF-α peptide (TBATP) is capable of suppressing the inhibitory effect on HUVECs induced by TNF-α, and is visualized by MRI after conjugating to super-paramagnetic Ce3/4+ cation-doped maghemite nanoparticles arising from ceric ammonium nitrate-mediated doping oxidation of starting magnetite nanoparticles (CAN-γ-Fe2 O3 NPs). Keywords: Peptide; Functional maghemite nanoparticles; Inner ear; Magnetic resonance imaging; Biological barrier. List of Abbreviations: CAN-γ-Fe2 O3 NPs: Super-paramagnetic maghemite (γ-Fe2 O3 ) nanoparticles using ceric ammonium nitrate (CAN)-mediated oxidation of starting magnetite (Fe3 O4 ) nanoparticles; HUVECs: Human umbilical vein endothelial cells; TNF-α: tumor necrosis factor-α.
|Journal of Materials Science and Nanotechnology,
|פורסם - 2017