# Design and Application of Cationic Nanocarriers to Inhibit Breast Cancer Progression in Primary and Metastatic Sites

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,036

## Abstract

PROJECT SUMMARY
Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen/progesterone receptors and
human epidermal growth factor receptor 2 (HER2) expression as well as its high rates of recurrence and
metastasis. Chemotherapy persists as one of the mainstays of breast cancer treatment, particularly for
triple-negative breast cancer. While chemotherapy is beneficial for killing the malignant tumor cells, it leads
to the release of damage-associated molecular patterns (DAMPs). DAMPs are a contributing factor to
cancer-related inflammation which can potentiate future metastatic spread through several mechanisms
such as the development of tumor microenvironments of metastasis (TMEM) sites. These DAMPs include
nucleic acids, cytokines, and proteins such as HMGB1. Polyamidoamine (PAMAM) is a biodegradable,
water-soluble dendrimer polymer with the ability to possess different charges and sizes depending on its
terminal branches and degree of branching (i.e. generation), respectively. Amine-terminated PAMAM is
positively charged (i.e. cationic) and can bind DNA and RNA. Building on this dendrimer, we have
synthesized modified cationic PAMAM-generation 3 (PAMAM-G3) derivatives that have decreased toxicity
and can encapsulate chemodrugs as nanoparticles and maintain the nucleic acid-binding property. Our
preliminary tests have shown that these materials can bind to both cell-free DNA and RNA released as a
result of treating triple-negative breast cancer cells with chemotherapy such as doxorubicin and paclitaxel.
In this research plan we aim to explore what other chemotherapy-induced DAMPs our materials can bind to
and suppress. The anti-metastatic effects of the materials will be studied using in-vitro and in-vivo models
as well as patient serum samples. A murine metastatic breast cancer model will serve as the basis for
assessing the effects of traditional chemotherapy delivery compared with chemotherapy delivery using
PAMAM-G3 nanoparticles with respect to primary tumor growth, degree of metastasis, and inflammatory
materials in mouse serum. In summary, we propose to pursue the specific aims of (1) Characterize
damage-associated molecular patterns (DAMPs) released from chemotherapy-treated TNBC cells;
(2) Determine the therapeutic efficacy of PAMAM-G3 scavenging polymers and nanoparticles on
immune system activation and invasive-potential caused by chemotherapy-induced DAMPs; and (3)
Understand the mechanisms behind PAMAM-G3 mediated DAMP scavenging. The experiments in this
proposal will contribute new knowledge on how chemotherapy influences the profile of circulating pro-
metastatic DAMPs. In addition, a novel method of dual chemotherapy delivery and DAMP scavenging via
modified PAMAM-G3 nanoparticles will be studied for its utility in reducing primary tumor and metastatic
burden. Completion of this proposal at Columbia University will provide the applicant with training in cancer
biology and engineering in medicine in preparatio...

## Key facts

- **NIH application ID:** 10142824
- **Project number:** 1F31CA257399-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Tolulope Olatokunbo Akinade
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142824

## Citation

> US National Institutes of Health, RePORTER application 10142824, Design and Application of Cationic Nanocarriers to Inhibit Breast Cancer Progression in Primary and Metastatic Sites (1F31CA257399-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142824. Licensed CC0.

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