# Development of an apoptosis biosensor for monitoring of breast cancer

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $502,136

## Abstract

Successful monitoring tumor response to neo-adjuvant chemotherapy (NAC) could offer the opportunity to tightly-
tailored individualized therapy in patients with breast cancer. Current treatment of breast cancer generally applies
a “one-size fits all” regardless of treatment success. The ability to monitor “on-treatment” response is critical for
both 1) the patients that have complete response and could benefit from reduced NAC to reduce morbidity and
2) to the patients who are not responding to current NAC to suggest a change in treatments which induce greater
anti-tumor response. Thus, the ability to reliably monitor tumor response to NAC treatment via an imaging-based
system is a vital step toward realizing patient-tailored therapy and would enable us to further move away from a
“one size fits all” paradigm in breast oncology. Therefore, we propose to develop a new Squaraine-based
biosensor (SAB) to identify apoptosis detectable using a new imaging technology, Multispectral Optoacoustic
Tomography (MSOT). As MSOT is a new imaging technology, exogenous reporter dyes are limited to 2 FDA
approved dyes, isosulfane blue and indocynaine green, neither of which can be conjugated to peptides. Our
objective is to: (1) develop a new optoacoustically optimized conjugatable reporter dye as part of the apoptosis
biosensor and (2) test the Squaraine apoptosis biosensor (SAB) in vivo to identify apoptosis following
chemotherapy treatment in vivo.
We propose to build upon our recent success of identifying tumors using multispectral optoacoustic tomography
combined with our expertise in NIR dye chemistry and molecular biology. To improve specificity of cell uptake of
the prototype SAB, we have included a portion of a cell penetrating peptide that is responsive to extracellular
acidic pH. We hypothesize that our lead prototype for the Squaraine Apoptosis Biosensor (SAB) will have
improved cell penetrating peptide (TS-CPP) and “turn on” at the apoptosis sequence, DEVD, to separate the
Squaraine dye from the QC1 dye, ultimately identifying apoptosis. To test our hypothesis, we propose the
following aims: 1) develop and characterize derivatives of prototype Squaraine to serve as the reporter for the
Squaraine apoptosis biosensor (SAB); 2) assess performance of optimized Squaraine and SAB as optoacoustic
agents in vitro; and 3) assess optimized SAB to facilitate detection of apoptosis in breast tumors in vivo using
multispectral optoacoustic tomography. Successful completion of these specific aims will develop an apoptosis
biosensor that ultimately could be used to identify apoptosis in vivo and clinically to monitor tumor response and
a new reporter dye detectable using optoacoustic imaging. Ultimately, this apoptosis biosensor would be well
suited for use as part of a multispectral contrast agent cocktail for identifying molecular features of disease.

## Key facts

- **NIH application ID:** 10851943
- **Project number:** 5R01EB034731-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Maged M Henary
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $502,136
- **Award type:** 5
- **Project period:** 2023-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851943

## Citation

> US National Institutes of Health, RePORTER application 10851943, Development of an apoptosis biosensor for monitoring of breast cancer (5R01EB034731-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10851943. Licensed CC0.

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