# Targeting the JAK/STAT3 Pathway in Triple-Negative Breast Cancer Using Biomimetic Nanoparticles

> **NIH NIH F31** · RICE UNIVERSITY · 2020 · $35,060

## Abstract

Project Summary/Abstract
Triple-negative breast cancer (TNBC) remains an ongoing clinical and therapeutic
challenge. Combining the absence of a targeted therapy and the higher risk of
metastasis and relapse, patients diagnosed with TNBC face a very poor prognosis. The
aggressive nature of this breast cancer sub-type has been attributed to the presence of
breast cancer stem cells (BCSCs) that possess the ability to self-renew and initiate
tumor growth, which are key drivers of metastases. The Janus kinase/signal transducer
and activator of transcription (JAK/STAT3) have been shown to not only be critical
nodes of this feature, but also overactive in TNBC. Targeting of this pathway using
inhibitors, either small-molecule drugs or siRNA, represents a promising treatment
method. However, delivery of these therapeutics requires the use of a drug delivery
system that is capable of overcoming the biological barriers posed by the body. To this
aim, nanoparticles have been widely explored as drug delivery vehicles that carry
cancer therapeutics to the tumor site. However, the success of these platforms has
been limited due to their rapid clearance by the immune system and non-specific
accumulation in other organs. This study aims to utilize a novel biomimetic leukocyte-
based nanoparticle platform (i.e. the leukosome) as a drug delivery vehicle to carry
therapeutics that target the JAK/STAT3 pathway in TNBC while overcoming the
aforementioned limitations of previously utilized nanoparticle systems. Leukosomes
loaded with inhibitors of this pathway will be synthesized and characterized, followed by
in vitro tests to determine the dose-response cell toxicity of drug-loaded particles, their
internalization and intracellular trafficking in TNBC cell lines and validate their
suppression of the JAK/STAT3 pathway. Finally, a patient-derived xenograft model of
TNBC will be utilized to determine the in vivo biodistribution of the leukosomes and
evaluate their therapeutic effects on tumor growth and the targeting of the BCSC
population. By combining the features of cell and cancer biology with the engineering of
fine-tuned nanoparticles, this platform will provide a novel solution to a currently unmet
clinical need in the treatment of TNBC.

## Key facts

- **NIH application ID:** 10003195
- **Project number:** 5F31CA232705-03
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Manuela Sushnitha
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $35,060
- **Award type:** 5
- **Project period:** 2018-09-15 → 2021-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003195

## Citation

> US National Institutes of Health, RePORTER application 10003195, Targeting the JAK/STAT3 Pathway in Triple-Negative Breast Cancer Using Biomimetic Nanoparticles (5F31CA232705-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10003195. Licensed CC0.

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