Related Experiment Video
Updated: Feb 12, 2026
Ligand-Mediated Nucleation and Growth of Palladium Metal Nanoparticles
Published on: June 25, 2018
Precise targeting of cancer metastasis using multi-ligand nanoparticles incorporating four different ligands
P M Peiris1, F He, G Covarrubias
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA. stathis@case.edu.
Abstract:
Metastasis displays a highly heterogeneous cellular population with cancer cells continuously evolving. As a result, a single-ligand nanoparticle cannot account for the continuously changing expression of targetable biomarkers over time and space. To effectively direct nanoparticles to metastasis, we developed a multi-ligand nanoparticle by using four different types of ligands on the same nanoparticle that target biomarkers on the endothelium associated with metastatic disease. These vascular targets included αvβ3 integrin, P-selectin, EGFR and fibronectin. Using terminal and in vivo imaging studies, the targeting performance of the multi-ligand nanoparticles was compared to the single-ligand nanoparticle variants. All four single-ligand nanoparticle variants achieved significant targeting of lung metastasis in the 4T1 mouse model of breast cancer metastasis with about 2.5% of the injected dose being deposited into metastasis. A dual-ligand nanoparticle resulted in a nearly 2-fold higher deposition into lung metastases than its single-ligand counterparts. The multi-ligand nanoparticle significantly outperformed its targeting nanoparticle counterparts achieving a deposition of ∼7% of its injected nanoparticles into lung metastases. Using the high sensitivity of radionuclide imaging, PET imaging showed that a multi-ligand nanoparticle labeled with [18F]fluoride was able to precisely target metastatic disease at its very early stage of development in three different animal models of metastatic breast cancer.
Insights
Developing multi-ligand nanoparticles effectively targets evolving metastatic disease. These nanoparticles precisely target early-stage metastasis, outperforming single-ligand variants for improved cancer imaging and therapy.
Area of Science:
- Nanotechnology
- Oncology
- Biomedical Imaging
Background:
- Metastasis is characterized by cellular heterogeneity and evolving biomarker expression.
- Single-ligand nanoparticles struggle to consistently target dynamic metastatic sites.
- Targeting endothelial biomarkers associated with metastatic disease is crucial for effective delivery.
Purpose of the Study:
- To develop and evaluate multi-ligand nanoparticles for enhanced targeting of metastatic disease.
- To compare the efficacy of multi-ligand nanoparticles against single-ligand variants in targeting lung metastasis.
- To assess the capability of multi-ligand nanoparticles for early-stage metastatic disease detection using PET imaging.
Main Methods:
- Development of multi-ligand nanoparticles functionalized with ligands targeting αvβ3 integrin, P-selectin, EGFR, and fibronectin.
- In vivo and terminal imaging studies using the 4T1 mouse model of breast cancer metastasis.
- Comparison of nanoparticle deposition in lung metastases between single-ligand, dual-ligand, and multi-ligand formulations.
- Positron Emission Tomography (PET) imaging with [18F]fluoride-labeled multi-ligand nanoparticles.
Main Results:
- Single-ligand nanoparticles achieved approximately 2.5% deposition in lung metastases.
- Dual-ligand nanoparticles showed a nearly 2-fold increase in deposition compared to single-ligand variants.
- Multi-ligand nanoparticles achieved approximately 7% deposition in lung metastases, significantly outperforming single-ligand counterparts.
- PET imaging demonstrated precise targeting of early-stage metastatic disease by multi-ligand nanoparticles in three distinct animal models.
Conclusions:
- Multi-ligand nanoparticles offer superior targeting efficiency for metastatic disease compared to single-ligand nanoparticles.
- The developed multi-ligand nanoparticle system demonstrates potential for precise imaging and therapeutic delivery to early-stage metastases.
- This approach addresses the challenge of evolving biomarker expression in metastatic cancer.
Related Concept Videos
02:40Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
02:40Ligand Binding Sites
02:51Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
00:49Ligand Binding and Linkage
00:49Ligand Binding and Linkage
00:43Complexometric Titration: Ligands