# Ionic Liquid-Coated NIR-II Polymer Conjugates as Targeted Brain Theranostics

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $542,484

## Abstract

PROJECT SUMMARY/ABSTRACT
There are currently limited treatments available to treat non-operable brain cancers, and none
that meaningfully extend the lifespan of patients. Imaging these diffuse tumors is also a challenge,
and current fluorescent probes emit in wavelengths with high biological background fluorescence.
This proposal describes the development of novel dye molecules that emit in the near-infrared II
(NIR-II)/shortwave infrared (SWIR) region (1000 – 2000 nm). Within the NIR-II/SWIR region,
higher resolution images are found at longer wavelengths. No small molecule emitters have peak
emission beyond 1400 nm and only one known molecule has peak emission >1250 nm. We have
preliminarily synthesized two fluorescent materials with emission maxima conservatively
projected at ~1700 nm and >1900 nm. These dyes offer the ability to see further into the SWIR
region than any other reported organic small molecules where image resolution is the highest.
Additionally, we proposed to synthesize materials with shorter wavelength emission than these
materials >2000 nm where imaging depth and contrast both are suggested to continually improve
based on the current literature. In order to effectively deliver the dye molecules into the brain, we
have to encapsulate them into nanocarriers. Linear-dendritic block-copolymers (LDBCs)
represent a highly functionalizable material for drug delivery vehicles. Its dual linear/dendritic
nature makes it excellent at encapsulating a variety of molecules. We use biocompatible ionic
liquids (ILs), molten salts comprised of asymmetric cations and anions, to `tune' the affinity of
nanoparticles to different cell types. Using this strategy, we have developed an IL that promotes
nanoparticle `hitchhiking' on erythrocytes to deliver them to the brain, and achieves cell-selective
targeting of microglia once delivered to the central compartment. Preliminary data in rats
demonstrate ~48% of injected nanoparticles accumulating in the brain within 6 hours, a vast
improvement over current nanoparticle delivery strategies. To this end, we will (Aim 1) generate
a library of novel NIR-II candidates, in addition to our current leads, that show peak emission at
1700 – 2000 nm, package them into LDBCs, and coat the nanoparticles with ILs. We will measure
their photophysical properties and confirm the preference that ILs confer to murine and human
blood components as potential cargo carriers. (Aim 2) We will assess the safety (subacute, acute,
subchronic, reproductive, mutagenic) and biodistribution of up to 5 leading formulations in rats,
and capture high-resolution live brain imaging. (Aim 3) Lead candidates (based on CNS
distribution and photophysical properties) will be assessed in vitro and in vivo in a xenografted
glioblastoma rat model.

## Key facts

- **NIH application ID:** 10588717
- **Project number:** 1R01EB034086-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Davita L. Watkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $542,484
- **Award type:** 1
- **Project period:** 2022-09-26 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10588717

## Citation

> US National Institutes of Health, RePORTER application 10588717, Ionic Liquid-Coated NIR-II Polymer Conjugates as Targeted Brain Theranostics (1R01EB034086-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10588717. Licensed CC0.

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