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Updated: Feb 3, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Imaging breast cancer using a dual-ligand nanochain particle
Gil Covarrubias1, Anthony Cha1, Abdelrahman Rahmy1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States of America.
Abstract:
Nanoparticles often only exploit the upregulation of a receptor on cancer cells to enhance intratumoral deposition of therapeutic and imaging agents. However, a single targeting moiety assumes that a tumor is homogenous and static. Tumoral microenvironments are both heterogenous and dynamic, often displaying variable spatial and temporal expression of targetable receptors throughout disease progression. Here, we evaluated the in vivo performance of an iron oxide nanoparticle in terms of targeting and imaging of orthotropic mouse models of aggressive breast tumors. The nanoparticle, a multi-component nanochain, was comprised of 3-5 iron oxide nanoparticles chemically linked in a linear chain. The nanoparticle's surface was decorated with two types of ligands each targeting two different upregulated biomarkers on the tumor endothelium, P-selectin and fibronectin. The nanochain exhibited improved tumor deposition not only through vascular targeting but also through its elongated structure. A single-ligand nanochain exhibited a ~2.5-fold higher intratumoral deposition than a spherical nanoparticle variant. Furthermore, the dual-ligand nanochain exhibited higher consistency in generating detectable MR signals compared to a single-ligand nanochain. Using a 7T MRI, the dual-ligand nanochains exhibited highly detectable MR signal within 3h after injection in two different animal models of breast cancer.
Insights
Dual-ligand nanochains improve iron oxide nanoparticle delivery to heterogeneous breast tumors. This dual targeting enhances MRI contrast agent deposition and detection for improved cancer imaging.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor microenvironments are heterogeneous and dynamic, with variable receptor expression.
- Conventional nanoparticles often rely on single receptor targeting, limiting efficacy.
- Targeting tumor endothelium offers an alternative strategy for nanoparticle delivery.
Purpose of the Study:
- To evaluate the in vivo performance of multi-component iron oxide nanochains for targeting and imaging aggressive breast tumors.
- To investigate the impact of dual-ligand functionalization on nanoparticle tumor deposition and MRI signal generation.
Main Methods:
- Synthesis of multi-component iron oxide nanochains functionalized with dual ligands (anti-P-selectin and anti-fibronectin).
- Evaluation of in vivo tumor targeting and deposition in orthotropic mouse models of breast cancer using 7T MRI.
- Comparison of dual-ligand nanochains with single-ligand nanochains and spherical nanoparticles.
Main Results:
- Dual-ligand nanochains demonstrated improved intratumoral deposition compared to spherical nanoparticles.
- The elongated structure of nanochains contributed to enhanced vascular targeting and tumor accumulation.
- Dual-ligand nanochains provided consistent and detectable MR signals within 3 hours post-injection in two breast cancer models.
Conclusions:
- Multi-component nanochains with dual-ligand targeting offer a promising strategy for enhanced nanoparticle delivery to heterogeneous tumors.
- This approach improves diagnostic imaging capabilities through consistent MRI signal generation.
- Dual-ligand functionalization overcomes limitations of single-target strategies in dynamic tumor microenvironments.
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