Tiwari P.M.Eroglu E.Bawage S.S.Vig K.Miller M.E.Pillai S.Dennis V.A.Singh S.R.2024-07-222024-07-22201401429612http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16943Reduced toxicity and ease of modification make gold nanoparticles (GNPs) suitable for targeted delivery, bioimaging and theranostics by conjugating cell-penetrating peptides (CPPs). This study presents the biodistribution and enhanced intracellular uptake of GNPs functionalized with VG-21, a CPP derived from vesicular stomatitis virus glycoprotein (G). Cell penetrating efficiency of VG-21 was demonstrated using CellPPD web server, conjugated to GNPs and were characterized using, UV-visible and FTIR spectroscopy, transmission electron microscopy, dynamic light scattering and zeta potential. Uptake of VG-21 functionalized GNPs (fGNPs) was tested in eukaryotic cell lines, HEp-2, HeLa, Vero and Cos-7, using flow cytometry, fluorescence and transmission electron microscopy (TEM), and inductively coupled plasmon optical emission spectroscopy (ICP-OES). The effects of nanoparticles on stress and toxicity related genes were studied in HEp-2cells. Cytokine response to fGNPs was studied invitro and invivo. Biodistribution of nanoparticles was studied in BALB/c mice using TEM and ICP-OES. VG-21, GNPs and fGNPs had little to no effect on cell viability. Upon exposure to fGNPs, HEp-2cells revealed minimal down regulation of stress response genes. fGNPs displayed higher uptake than GNPs in all cell lines with highest internalization by HEp-2, HeLa and Cos-7cells, in endocytotic vesicles and nuclei. Cytokine ELISA showed that mouse J774cells exposed to fGNPs produced less IL-6 than did GNP-treated macrophage cells, whereas TNF-α levels were low in both treatment groups. Biodistribution studies in BALB/c mice revealed higher accumulation of fGNPs than GNPs in the liver and spleen. Histopathological analyses showed that fGNP-treated mice accumulated 35ng/mg tissue and 20ng/mg tissue gold in spleen and liver respectively, without any adverse effects. Likewise, serum cytokines were low in both GNP- and fGNP-treated mice. Thus, VG-21-conjugated GNPs have enhanced cellular internalization and are suitable for various biomedical applications as nano-conjugates. © 2014 The Authors.EnglishAll Open Access; Hybrid Gold Open AccessAnimalsCell SurvivalCell-Penetrating PeptidesCercopithecus aethiopsCOS CellsFemaleGoldHeLa CellsHumansInterleukin-6Membrane GlycoproteinsMetal NanoparticlesMiceMice, Inbred BALB CMicroscopy, Electron, TransmissionTissue DistributionTumor Necrosis Factor-alphaVero CellsVesiculovirusViral Envelope ProteinsEukaryotaMusVesicular stomatitis virusCell cultureCytologyDrug deliveryElectromagnetic inductionElectron microscopyEmission spectroscopyFiber optic sensorsFourier transform infrared spectroscopyGenesGoldLight scatteringMammalsMedical applicationsMetal nanoparticlesMobile securityNanoparticlesOptical emission spectroscopyPeptidesTissueTissue engineeringToxicityTransmission electron microscopyVirusescell penetrating peptidecytokinedrug vehiclegold nanoparticleinterleukin 6nanoconjugatenanoparticleprotein VG 21protein VG 21 gold nanoparticle conjugatetumor necrosis factor alphaunclassified drugcell penetrating peptideG protein, vesicular stomatitis virusgoldinterleukin 6membrane proteinmetal nanoparticletumor necrosis factor alphavirus envelope proteinCell penetrating peptides (CPPs)Cell-penetrating peptideCellular internalizationFunctionalized gold nanoparticlesGold nanoparticles (GNPs)Histopathological analysisIntracellular translocationVesicular stomatitis virusanimal cellanimal experimentanimal tissueArticlecell nucleuscell viabilitycontrolled studyCOS 7 cell linecytokine productiondrug accumulationdrug conjugationdrug delivery systemdrug distributiondrug effectdrug transportendosomeenzyme linked immunosorbent assayflow cytometryfluorescence microscopygene expressionHeLa cell lineHEp 2 cell linehistopathologyhumanhuman cellin vitro studyin vivo studyinductively coupled plasmon optical emission spectroscopyinfrared spectroscopyinternalizationlight scatteringlivermacrophagemass spectrometrymousenonhumanoxidative stresspriority journalspleentissue distributiontransmission electron microscopyultraviolet spectroscopyVero cell lineVesiculoviruszeta potentialanimalBagg albino mousecell survivalchemistryChlorocebus aethiopsCOS 1 cell linedrug effectsfemalemetabolismVesiculovirusCellsArticle10.1016/j.biomaterials.2014.07.032