# Copper-depleting nanotheranostics for treating triple negative breast cancer

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $200,714

## Abstract

ABSTRACT
Breast cancer is the number two cause of death among all types of cancers in women. The deadliest subtype
of breast cancer, triple-negative, carries the highest metastatic risk and poorest outcome due to the resistance
to current therapeutic methods. Triple-negative breast cancer (TNBC) is an intrinsically heterogeneous disease.
Targeting single biomarker or oncogene often yields unsatisfactory therapeutic outcome in TNBC treatment. To
achieve a broader therapeutic benefit, our starting point is copper ion, one critical metal ion that plays
irreplaceable roles in a broad range of biochemical reactions. Copper excess in serum and cancerous tissues
has been long recognized in breast cancer patients. Dysregulation of copper metalloproteins is found to be
involved in uncontrolled growth, invasion, dissemination of cancer cells, angiogenesis and secondary tumor
formation at distant sites. Despite the well-recognized importance, successful attempts to treat cancer with
copper chelation are rather limited.
Our parent R01 project aims to establish a self-reporting copper depletion nanoplatform to effectively deplete
copper in TNBC and ultimately inhibit primary tumor progression and metastasis formation through designing
copper-depleting nanocomplex with high depleting efficiency, low toxicity and self-reporting function as TNBC
theranostics (Aim 1), determining the treatment effect of copper-depleting nanocomplex and identify the
therapeutic mechanism in vitro (Aim 2), and defining the therapeutic efficacy of copper-depleting nanocomplex
for primary and metastatic TNBC tumor models (Aim 3).
In response to the RFA-CA-21-007, this revision application will introduce the cutting-edge technology on
mitochondria isolation and characterization to scrutinize the mitochondria-related cellular function alterations
after the CDN treatment (e.g. apoptosis and metabolism) and reveal basic mechanistic insights into how
mitochondrial heterogeneity may contribute to the resistance to copper depletion treatment (new Aim 4). The
research will be a collaborative effort between the PI of the parent R01 and Professor Peter J Burke from
University of California-Irvine, the developer of the mitochondrial analysis techniques through the IMAT funding
to apply the IMAT technology for the analysis of function of single mitochondrion upon copper depletion. This
R01-IMAT unity will largely extend current understanding of the biology associated with copper depletion and
help expand the scope of parent R01 to other cancer types beyond TNBC.

## Key facts

- **NIH application ID:** 10413265
- **Project number:** 3R01CA243033-03S1A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jianghong Rao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,714
- **Award type:** 3
- **Project period:** 2019-09-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413265

## Citation

> US National Institutes of Health, RePORTER application 10413265, Copper-depleting nanotheranostics for treating triple negative breast cancer (3R01CA243033-03S1A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10413265. Licensed CC0.

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