# Continuous Probing of Nanoconstruct-Cell Interactions at Biologically Relevant Time Scales

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $197,282

## Abstract

PROJECT SUMMARY
 This proposal aims to develop live-cell, multi-channel imaging tools that can visualize—continuously, and in
real time—nanoparticle interactions with cellular components. We will focus on several different time windows,
where early time periods will monitor nanoparticle-cell membrane binding and uptake and later times will track
endosomal accumulation and escape. The ability to resolve temporally and spatially how particle size/shape and
ligand density affects interactions in 3D is critical for determining structure-activity-relationships and mechanism
of action in live cells. To characterize interactions of functional nanoparticles with different cellular structures at
physiologically relevant times, we propose to design a multi-channel optical microscope integrated with an opto-
splitter and custom live-cell imaging chamber. Simultaneous images can be acquired in different channels of the
fluorescence of dye-labeled organelles and dye-labeled ligands on the particles as well as differential
interference contrast (DIC) signals of whole cells, cellular components, and nanoparticle cores. Correlation of
structural and functional images provides a powerful window into how local nanoconstruct interactions can
mediate a biological response. For model systems, we will compare gold nanoconstructs with oligonucleotide
ligand shells of both targeting (DNA aptamers) or non-targeting (siRNA) properties. Nanoparticle shape enables
a unique handle to probe rotation and orientation of intracellular particle interactions. This work can bridge a gap
in understanding the behavior of nanoconstructs intracellularly and how the integrity and presentation of
oligonucleotides in ligand shells affects targeting and other processes such as endosomal escape, which is
critical to assess therapeutic efficacy.

## Key facts

- **NIH application ID:** 10475700
- **Project number:** 5R01GM131421-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Teri Wang Odom
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $197,282
- **Award type:** 5
- **Project period:** 2019-09-27 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475700

## Citation

> US National Institutes of Health, RePORTER application 10475700, Continuous Probing of Nanoconstruct-Cell Interactions at Biologically Relevant Time Scales (5R01GM131421-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10475700. Licensed CC0.

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