# Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $405,116

## Abstract

The goal of this project is to develop smart targeted lipid ECO/siRNA nanoparticles (ELNP) to target
oncogenic long non-coding RNAs (lncRNAs) as a novel therapy to treat triple-negative breast cancer
(TNBC). Metastasis and drug resistance are the main causes for the high mortality rates of women
diagnosed with TNBC worldwide. Although targeted therapies have been developed to treat some
subtypes of breast cancer, the TNBC subtype is particularly refractory to these therapies. Oncogenic
lncRNAs play a critical role in tumorigenesis, metastasis, drug resistance, and immune suppression of
cancer by simultaneously manipulating multiple cancer-associated signaling pathways. We have
demonstrated in this project that onco-lncRNAs are promising therapeutic targets to treat TNBC, and
that downregulation of an onco-lncRNA with systemic delivery of targeted ECO/siRNA nanoparticles
results in significant suppression of TNBC proliferation. We have identified a novel lncRNA BORG,
which is associated with TNBC development, metastasis, drug resistance and immune invasion, as a
compelling therapeutic target to treat TNBC. It is overexpressed in invasive BC, including TNBC, but
not in normal tissues. Downregulation of BORG with targeted ECO/siRNA nanoparticles has potential
to inhibit metastasis, sensitize TNBC to chemotherapy, and enhance antitumor immunity for curative
treatment of TNBC. In this project, we will optimize and develop the smart ECO/siBORG nanoparticles
to efficiently deliver siBORG in TNBC to silence the cancer-promoting lncRNA. We will also explore
the combination therapy of silencing BORG with a tumor-specific peptide drug conjugate and/or
immunotherapy to treat TNBC and to eventually eradicate this deadly disease. The specific aims of
this project are 1) to optimize and develop smart siBORG-ELNP for efficient and specific gene
silencing in breast cancer cells; 2) to determine the efficacy of targeted siBORG-ELNP as single
therapy and in combination with targeted chemotherapy in animal TNBC models; and 3) to determine
the efficacy of targeted siBORG-ELNP in modulating TIME for improved immunotherapy in animal
TNBC models. Our long-term goal is to develop a novel and feasible therapy based on the smart
nanoparticles to treat life-threatening breast cancer.

## Key facts

- **NIH application ID:** 10812121
- **Project number:** 2R01CA235152-06
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** ZHENG-RONG LU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $405,116
- **Award type:** 2
- **Project period:** 2018-12-12 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812121

## Citation

> US National Institutes of Health, RePORTER application 10812121, Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy (2R01CA235152-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10812121. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*