This application is in response to the RFA-ES-06-008: Manufactured nanomaterials: Physicochemical principles of biocompatibility and toxicity. Recent advances in nanotechnology have enabled fabrication of novel nanoconstructs with potential commercial and biomedical applications. Some promising nanoconstructs include dendrimers and silica nanoparticles. These nanoconstructs can be fabricated with discrete, well-defined monodisperse size, shape and surface properties. However little is known about the interactions of these particles with mammalian systems including their potential to cause toxicity. The focus of this application is on systematically evaluating the influence of size, geometry, porosity and surface functionality of dendritic as well as silica nanoparticles on their toxicity and cellular uptake.
Three Specific Aims are proposed: 1. Preparation and characterization of dendrimers, porous silica nanoparticles, and silica nanotubes with discrete variations in size, charge and surface chemistry to regulate biocompatibility. 2. In vitro evaluation of toxicity, biocompatibility and mechanisms of uptake of the prepared nanomaterials as a function of physicochemical properties. 3. In vivo evaluation of biodistribution and pharmacokinetics of the nanomaterials and their subsequent correlation with physicochemical properties, toxicity and biocompatibility.
| Hadipour Moghaddam, Seyyed Pouya; Yazdimamaghani, Mostafa; Ghandehari, Hamidreza (2018) Glutathione-sensitive hollow mesoporous silica nanoparticles for controlled drug delivery. J Control Release 282:62-75 |
| Astashkina, Anna I; Jones, Clint F; Thiagarajan, Giridhar et al. (2014) Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model. Biomaterials 35:6323-31 |
| Herd, Heather; Daum, Nicole; Jones, Arwyn T et al. (2013) Nanoparticle geometry and surface orientation influence mode of cellular uptake. ACS Nano 7:1961-73 |
| Thiagarajan, Giridhar; Sadekar, Shraddha; Greish, Khaled et al. (2013) Evidence of oral translocation of anionic G6.5 dendrimers in mice. Mol Pharm 10:988-98 |
| Moos, Philip J; Honeggar, Matthew; Malugin, Alexander et al. (2013) Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications. Mol Pharm 10:3242-52 |
| Thiagarajan, Giridhar; Greish, Khaled; Ghandehari, Hamidreza (2013) Charge affects the oral toxicity of poly(amidoamine) dendrimers. Eur J Pharm Biopharm 84:330-4 |
| Sadekar, S; Linares, O; Noh, Gj et al. (2013) COMPARATIVE PHARMACOKINETICS OF PAMAM-OH DENDRIMERS AND HPMA COPOLYMERS IN OVARIAN-TUMOR-BEARING MICE. Drug Deliv Transl Res 3:260-271 |
| Jones, Clinton F; Campbell, Robert A; Brooks, Amanda E et al. (2012) Cationic PAMAM dendrimers aggressively initiate blood clot formation. ACS Nano 6:9900-10 |
| Sadekar, S; Ghandehari, H (2012) Transepithelial transport and toxicity of PAMAM dendrimers: implications for oral drug delivery. Adv Drug Deliv Rev 64:571-88 |
| Greish, Khaled; Thiagarajan, Giridhar; Ghandehari, Hamidreza (2012) In vivo methods of nanotoxicology. Methods Mol Biol 926:235-53 |
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