# A Wholly Protein-based Self-assembly Nanoplatform for TNBC-specific Combination Therapy

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $473,654

## Abstract

Abstract
 Triple-negative breast cancer (TNBC) is a unique type of breast cancer that does not express or
overexpress estrogen receptor (ER), progesterone receptor (PR), and HER2. During the past several decades,
the standard care of TNBC remains the highly toxic chemotherapy with little progress in more effective treatments.
To address the urgent unmet need to develop targeted therapies specific for TNBC, we developed a totally
protein-based nanoplatform called ProNano that is composed of two recombinant proteins, including the first an
elastin-like polypeptide (ELP) nanocore that displays multiple calmodulin-binding short peptides on the surface,
and the second a recombinant calmodulin protein genetically fused with a highly stable and modular protein
domain possessing either tumor homing or therapeutic features. The docking of the ELP nanocore with a TNBC-
targeting module together with a functional module with therapeutic feature results in bifunctional ProNanos that
can be used for tumor-homing delivery of therapeutic agents for the combination therapy for TNBC. Three
specific aims will be pursued in this project. The first specific aim is to develop a ProNano platform that allows
tunable targeting of TNBC cells based on their surface antigen expression profiles. The second specific aim is
to develop a bifunctional ProNano platform that allows tumor-specific blockade of the aberrant Wnt signaling for
the treatment of TNBC. The third specific aim is to develop a bifunctional ProNano platform that allows tumor-
specific inhibition of the ENPP1-catalyzed hydrolysis of extracellular cGAMP for combination immunotherapy of
TNBC. The bifunctional ProNano platforms developed in this project have several major advantages over
conventional nanoplatforms, including all protein components each can be precisely and genetically engineered,
oriented and self-assembled introduction of both tumor homing and/or therapeutic moieties at desired ratios
without need of any chemical conjugation, and use of highly stable and easily expressed modular polypeptides
with no or low immunogenicity. Although we focus on the targeted treatment for TNBC, the ProNano platforms
developed in this project can be easily adapted to address other cancer types simply by changing the tumor
targeting module.

## Key facts

- **NIH application ID:** 10423223
- **Project number:** 1R01EB032865-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Rihe Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $473,654
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10423223

## Citation

> US National Institutes of Health, RePORTER application 10423223, A Wholly Protein-based Self-assembly Nanoplatform for TNBC-specific Combination Therapy (1R01EB032865-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10423223. Licensed CC0.

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