# Deep-tissue targeted molecular imaging with a palette of NIR-II emissive DNA-stabilized nanoclusters

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $1,249,099

## Abstract

Project summary/abstract
Advances in in vivo biomedical imaging are critical for revolutionizing the ability of researchers
and clinicians to peer inside the living body. These advances often catalyze major steps forward
in our understanding of biomolecular and physiological processes. At present, the power of
fluorescence imaging for deep tissue biomedical imaging is limited by the relative opacity of
biological tissues and fluids at visible to short near-infrared wavelengths < 1,000 nm. The NIR-II
tissue transparency window (1,000 to 1,700 nm) presents the opportunity to achieve molecular
fluorescence imaging at centimeter-scale depths, for monitoring biomolecular processes at high
spatial resolutions and in real time. To fully realize the transformative potential of NIR-II
fluorescence deep tissue imaging, we must develop fluorophores that overcome major challenges
of existing organic dyes and nanoparticles with NIR-II emission, such as low brightness, large
size, low solubility, and toxicity. This proposed research program pioneers a new approach to
develop small, bright, tunable, and biocompatible NIR-II emitters for targeted molecular imaging
in vivo. We will exploit a novel class of NIR-emissive DNA-stabilized silver nanoclusters (AgN-
DNAs) with 1-3 nm sizes, high-quantum yield emission, tunable fluorescence colors, and
compatibility with nucleic acid chemistries. Recent experiments have uncovered the first AgN-
DNAs with NIR-II emission and support the promise of creating a palette of these nanoclusters
that emit throughout the NIR-II spectral region. Using high-throughput experimental screening
and machine learning approaches, we will develop a set of bright, stable, and NIR-II emitting AgN-
DNAs that are well-suited for in vivo imaging. In tandem, we will develop chemical strategies to
transform these nanoclusters into biolabels for targeted molecular imaging by conjugating AgN-
DNAs to aptamers, peptides, antibodies, and other biomolecules of interest. These hybrid
biolabels will enable targeted staining and NIR-II fluorescence imaging of tumors, organs, and
other targets. The utility of the new NIR-II biolabels for fluorescence imaging will be assessed in
tissue models and then tested in vivo in mouse models for vascular imaging and for tracking novel
breast cancer therapeutics. We envision that these new fluorescent probes will enable a new era
of deep tissue fluorescence imaging, with a versatile range of applications from cancer research
and therapeutics development to microvascular imaging.

## Key facts

- **NIH application ID:** 10910692
- **Project number:** 1DP2EB037187-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Stacy Marla Copp
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,249,099
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910692

## Citation

> US National Institutes of Health, RePORTER application 10910692, Deep-tissue targeted molecular imaging with a palette of NIR-II emissive DNA-stabilized nanoclusters (1DP2EB037187-01). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10910692. Licensed CC0.

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