# BIOLOGICAL FATE AND BIOCOMPATIBILITY OF SILICA-BASED NANOCONSTRUCTS

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $480,633

## Abstract

PROJECT SUMMARY
 A major challenge with systemic administration of silica nanoparticles (SNPs) is clearance by and
accumulation in organs of mononuclear phagocytic system (MPS), and subsequent immune response. Poor
loading capacity of SNPs, their stability and vacuolization in macrophages, and potentially lower metabolism and
clearance rates in patient populations may necessitate administration of high and frequent doses of SNPs which
could lead to MPS saturation and overload. Detailed investigation of immunotoxicity of SNPs in the MPS is
needed to establish their safety profile to choose drug carriers with well-defined immunological properties. The
influence of SNPs on the fate and function of phagocytes after uptake and saturation, and on host immune
response need further elucidation. The correlation between the physicochemical properties of SNPs and the
mechanisms of sex-dependent toxicity is unclear. Also, the immune response alteration upon i.v. administration
of SNPs and the mechanisms behind this response are largely unknown. To address these knowledge gaps in
this grant application the following Specific Aims are proposed:
 1) To investigate the influence of saturation of macrophages with SNPs on their phagocytic activity,
survival, proliferation, and immune signaling as a function of nanoparticle physicochemical properties. The
underlying hypothesis to be tested in this aim is that saturation of macrophages by SNPs will influence their
normal function, molecular signaling, and fate based on nanoparticle characteristics.
 2) To investigate bone marrow toxicity and function of tissue-resident macrophages after i.v.
administration of SNPs, and assess the number and activation status of circulating phagocytes after in vitro
exposure to SNPs. The underlying hypothesis to be tested in this aim is that size, geometry, and porosity of
SNPs influence the normal function of bone marrow, tissue-resident macrophages, and peripheral blood
phagocytes, a phenomenon which may be reversible and depend on dose and frequency of administration.
 3) To investigate the immune side effects and anti-PEG response of systemically administered SNPs as
a function of animal sex and particle physicochemical properties. The underlying hypotheses are: i) Anti-PEG
IgM and IgG will be generated in a time-dependent manner upon exposure to PEGylated SNPs; ii) variation in
immune response in female vs male Th1 and Th2 bias animal models will contribute to SNP toxicity and immune-
mediated side effects.
 This proposal is significant because understanding key physicochemical properties of SNPs with well-
defined immunological properties will help establish safer platforms for intravenous drug delivery. It is innovative
because for the first time it approaches different SNP interactions with various components of the immune system
as a result of animal-sex and different immune-biased in a systematic fashion.

## Key facts

- **NIH application ID:** 10357023
- **Project number:** 2R01ES024681-11A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Hamid Ghandehari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $480,633
- **Award type:** 2
- **Project period:** 2007-09-28 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357023

## Citation

> US National Institutes of Health, RePORTER application 10357023, BIOLOGICAL FATE AND BIOCOMPATIBILITY OF SILICA-BASED NANOCONSTRUCTS (2R01ES024681-11A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357023. Licensed CC0.

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