# Impact of Fn14-targeted Nanoparticles for Triple-Negative Breast Cancer

> **NIH NIH R37** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $353,419

## Abstract

Project Summary and Abstract
Triple-negative breast cancer (TNBC) - an aggressive subtype of breast cancer that is associated with increased
metastatic potential and poor patient survival - is characterized by the lack of expression of estrogen receptor
(ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) and accounts for ~15-
20% of invasive breast cancers. TNBC represents an important clinical challenge because these cancers
respond poorly to endocrine therapy or other available targeted agents; thus, chemotherapy is currently the
backbone of standard therapy with a median survival of only ~13 months. Current FDA-approved nanoparticle-
drug formulations of doxorubicin (Doxil) and paclitaxel (Abraxane) have been studied for the treatment of TNBC,
however neither have been shown to significantly improve tumor control or patient survival. This is most likely
due to (i) limited extravasation from the tumor vasculature, (ii) poor penetration within breast tumor tissue, (iii)
inability to efficiently target tumor cell drug uptake within the tumor microenvironment, and (iv) development of
drug resistance via expression of multidrug resistance (MDR) pumps such as P-glycoprotein. To address these
therapeutic barriers, we have recently: (1) engineered relatively large polymeric nanoparticles (between 63 to
114 nm) that rapidly penetrate in breast tumor tissue with tumor-specific fibroblast growth factor-inducible 14
(Fn14)-targeting to further improve particle dispersion, drug distribution, and tumor-specific cellular uptake within
the tumor microenvironment and (2) developed a novel high-throughput method for quantitative characterization
of Fn14-specific and nonspecific binding (towards tumor ECM) of various nanoparticle formulations. Thus, the
central hypothesis of this grant proposal is that by modulating the Fn14-specific equilibrium binding affinities (KD)
and minimizing the nonspecific binding to tumor ECM, Fn14-targeted tumor penetrating nanoparticles will (1)
provide well-dispersed, sustained delivery into the tumor and regions of the tumor tissue that contain TNBC cells
and (2) specifically target to and efficiently traffic within Fn14-positive TNBC cells while sparing adjacent healthy
tissues from toxic effects. This strategy is likely to result in significant improvements in efficacy and reduce toxicity
in TNBC primary tumors and disseminated metastases, compared to free drugs and their clinical nanoparticle
formulation counterparts, which will generate new insights into the rate-limiting barriers and mechanisms of
tumor-specific targeting for nanoparticle therapeutics. Future applications of the information obtained from this
project may be applied to improve the delivery and therapeutic efficacy of molecularly targeted drugs and drug
combinations, which has the potential to eventually translate into novel, more effective treatment strategies.
Importantly, the successful development of effective nanoparticle ...

## Key facts

- **NIH application ID:** 9868898
- **Project number:** 5R37CA218617-03
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Anthony J. Kim
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $353,419
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868898

## Citation

> US National Institutes of Health, RePORTER application 9868898, Impact of Fn14-targeted Nanoparticles for Triple-Negative Breast Cancer (5R37CA218617-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9868898. Licensed CC0.

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