# Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $23,693

## Abstract

3.8.1 Research, mentoring and career development
1). Research Plan
1.1). Abstract of the parent grant
 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:** 10307922
- **Project number:** 3R01CA235152-03S1
- **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:** $23,693
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307922

## Citation

> US National Institutes of Health, RePORTER application 10307922, Smart nanoparticles regulating oncogenic IncRNA for breast cancer therapy (3R01CA235152-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10307922. Licensed CC0.

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