# Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $357,780

## Abstract

The goal of this project is to develop smart dual-targeted lipid ECO/siRNA self-assembly
nanoparticles to target oncogenic long non-coding RNAs (lncRNAs) as a novel therapy to
treat metastatic and drug-resistant triple negative breast cancer (TNBC). Metastasis and drug
resistance are the main causes for high mortality rate of women diagnosed with TNBC
worldwide. Although targeted therapies have been developed to treat some subtypes of
breast cancer, the TN subtype is particularly refractory to these therapies. Oncogenic
lncRNAs play a critical role in tumorigenesis, stemness, invasion, metastasis, and drug
resistance of cancer by simultaneously manipulating multiple cancer-associated signaling
pathways. Hence, lncRNAs are promising novel therapeutic targets for TNBC. We will
develop smart dual-targeted lipid ECO/siRNA nanoparticles to regulate the expression of an
identified lncRNA associated with cancer EMT, stemness, metastasis, and drug resistance as
a novel therapy for TNBC. This oncogenic lncRNA is highly expressed in TNBC tumors, but
not in normal tissues, making this smart nanoparticle therapy a highly feasible and promising
approach to effectively treating TNBC without any adverse effects in healthy tissues. We have
demonstrated the feasibility of silencing the oncogenic lncRNA for suppressing the survival
and aggressiveness of TNBC cells and for completely inhibiting tumor proliferation in a TNBC
mouse model. In this project, we will optimize and develop the smart ECO/siRNA
nanoparticles to improve tumor-specific cytosolic delivery of therapeutic siRNAs and to
effectively silence the cancer-promoting lncRNA in treating TNBC. We will also explore the
combination therapy of silencing lncRNA with the smart nanoparticles and chemotherapy to
have the synergistic effects of inhibiting metastasis, alleviating multidrug resistance and
enhancing chemotherapy to achieve curative outcomes and to eventually eradicate TNBC.
The specific aims of this project are 1) to design and optimize smart dual-targeted
ECO/siRNA nanoparticles for efficient and specific gene silencing in cancer cells via systemic
administration; 2) to determine the effects of silencing oncogenic lncRNA with the smart dual-
targeted ECO/siRNA nanoparticles on the invasiveness and drug-resistance of TNBC cells in
vitro; 3) to determine the efficacy of the smart dual-targeted ECO/siRNA nanoparticles alone
and in combination with chemotherapy for TNBC therapy in animal models. Our long-term
goal is to develop a novel and feasible therapy based on the smart nanoparticles to treat life-
threatening metastatic and drug-resistant breast cancer.

## Key facts

- **NIH application ID:** 10054176
- **Project number:** 5R01CA235152-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** ZHENG-RONG LU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $357,780
- **Award type:** 5
- **Project period:** 2018-12-12 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054176

## Citation

> US National Institutes of Health, RePORTER application 10054176, Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy (5R01CA235152-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10054176. Licensed CC0.

---

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