The global goal of this project is to assess how physicochemical characteristics of nanomaterials modulate biological environmental responses. In this application the influence of porosity, degradation and curvature of silica nanoparticles (SNPs) on mechanisms of cellular uptake, biodistribution, pharmacokinetics and toxicity will be examined. Specifically, we will examine in more detail the cellular fate and mechanisms of intracellular transport of the SNPs, how inflammatory responses are initiated in response to the changes in the physicochemical properties, and what would be the biological fate of degradation products of SNPs.
Three Specific Aims are proposed: 1) 1. Synthesis and characterization of SNPs with systematic differences in size, porosity, surface roughness and functionality, and biodegradability, 2) Investigate how surface properties affect protein and cellular inflammatory mediated mechanisms in vitro, 3) Investigate chronic inflammatory mediated mechanisms as a function of surface properties in vivo.

Public Health Relevance

Nanomaterials are increasingly used in biomedical applications. A detailed understanding of potential mechanisms of toxicity of such materials as a function of their structure will provide guidelines for development of safe engineered structures.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Nanotechnology Study Section (NANO)
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Nadadur, Srikanth
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University of Utah
Schools of Pharmacy
Salt Lake City
United States
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Gao, Zhe; Hadipour Moghaddam, Seyyed Pouya; Ghandehari, Hamidreza et al. (2018) Synthesis of water-degradable silica nanoparticles from carbamate-containing bridged silsesquioxane precursor. RSC Adv 8:4914-4920
Yazdimamaghani, Mostafa; Moos, Philip J; Ghandehari, Hamidreza (2018) Global gene expression analysis of macrophage response induced by nonporous and porous silica nanoparticles. Nanomedicine 14:533-545
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
Hadipour Moghaddam, Seyyed Pouya; Saikia, Jiban; Yazdimamaghani, Mostafa et al. (2017) Redox-Responsive Polysulfide-Based Biodegradable Organosilica Nanoparticles for Delivery of Bioactive Agents. ACS Appl Mater Interfaces 9:21133-21146
Zeller Meidell, Krystin; Robinson, Ryan; Vieira-de-Abreu, Adriana et al. (2017) RGDfK-functionalized gold nanorods bind only to activated platelets. J Biomed Mater Res A 105:209-217
Anchordoquy, Thomas J; Barenholz, Yechezkel; Boraschi, Diana et al. (2017) Mechanisms and Barriers in Cancer Nanomedicine: Addressing Challenges, Looking for Solutions. ACS Nano 11:12-18
Mohammadpour, Raziye; Safarian, Shahrokh; Buckway, Brandon et al. (2017) Comparative Endocytosis Mechanisms and Anticancer Effect of HPMA Copolymer- and PAMAM Dendrimer-MTCP Conjugates for Photodynamic Therapy. Macromol Biosci 17:
Jones, David E; Lund, Albert M; Ghandehari, Hamidreza et al. (2016) Molecular dynamics simulations in drug delivery research: Calcium chelation of G3.5 PAMAM dendrimers. Cogent Chem 2:
Saikia, Jiban; Yazdimamaghani, Mostafa; Hadipour Moghaddam, Seyyed Pouya et al. (2016) Differential Protein Adsorption and Cellular Uptake of Silica Nanoparticles Based on Size and Porosity. ACS Appl Mater Interfaces 8:34820-34832
Yellepeddi, Venkata K; Ghandehari, Hamidreza (2016) Poly(amido amine) dendrimers in oral delivery. Tissue Barriers 4:e1173773

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