# Development of a Theranostic Nanomedicine Construct for Ovarian Cancer

> **NIH NIH R21** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $390,858

## Abstract

RELEVANCE: Ovarian cancer is the fifth leading cause of cancer-related deaths for women in the United States.
While ovarian cancer patients initially respond to current treatment options, most patients will eventually relapse
and develop drug-resistant disease. Our goal is to develop a theranostic that can detect and stage ovarian cancer
while also acting as a systemic radiotherapeutic delivery platform. It is envisioned that the development of the
technologies in this proposal would allow for the administration of higher therapeutic doses as well as lead to an
increase in the efficacy, safety and potential of these agents, and other drug delivery systems, for clinical
translation.
OBJECTIVE/HYPOTHESIS: The objective of this proposal is to develop a pretargeted theranostic platform that
synergistically builds upon our work with MPS-evading, HPMA copolymers as well as take advantage of the
tremendous potential of IEDDA chemistry. We hypothesize that the MPS-evading, HPMA copolymers can serve
as a unique platform to exploit these transformative in vivo conjugation technologies in the development of a
novel radiotherapeutic agent for ovarian cancer.
SPECIFIC AIMS: (1) Optimize the EPR-targeted, MPS-evading, HPMA Copolymers: Investigate/Optimize
Factors that Influence In Vitro/In Vivo Performance; (2) Investigate and Optimize Small Molecule
Radiotherapeutic TZs for In Vivo Targeting/Conjugation to Pretargeted HPMA Copolymer Platform.
STUDY DESIGN: In this application, we propose to develop a theranostic platform composed of two
components: 1) a pretargeted diagnostic HPMA copolymer capable of targeting tumors through the EPR effect
and the Gastrin-Releasing Peptide Receptor (GRPR), while clearing efficiently from non-target tissues and 2) a
radiotherapeutic chaser agent that, using IEDDA chemistry, will be captured by the tumor-associated pretargeted
copolymer. In the first aim, we propose to optimize the TCO-incorporation and the GRPR-targeting vector density
of the HPMA copolymer to achieve the desired biological performance. Simultaneously, in the second aim,
investigations of the chaser agent will be performed. In these studies, the impact of the hydrophilicity of the TZ
moiety will be explored. Lastly, the optimized components will be investigated using patient-derived xenograft
mouse models of ovarian cancer.

## Key facts

- **NIH application ID:** 10218729
- **Project number:** 1R21CA249819-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Jered C Garrison
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,858
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218729

## Citation

> US National Institutes of Health, RePORTER application 10218729, Development of a Theranostic Nanomedicine Construct for Ovarian Cancer (1R21CA249819-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218729. Licensed CC0.

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