Precise targeting of cancer metastasis using multi-ligand nanoparticles incorporating four different ligands
| Autor: | Oguz Turan, Felicia He, B. Gnanasambandam, S. Raghunathan, C. Wu, Pubudu M. Peiris, Gil Covarrubias, Morgan E Lorkowski, William P Schiemann, Efstathios Karathanasis |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Population Nanoparticle Breast Neoplasms Ligands Article Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Biomarkers Tumor medicine Animals Humans General Materials Science Neoplasm Metastasis education education.field_of_study biology Chemistry medicine.disease Metastatic breast cancer Fibronectin Disease Models Animal 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Nanoparticles Preclinical imaging |
| Zdroj: | Nanoscale. 10:6861-6871 |
| ISSN: | 2040-3372 2040-3364 |
| DOI: | 10.1039/c8nr02513d |
| Popis: | 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 α(v)β(3) 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 [(18)F]fluoride was able to precisely target metastatic disease at its very early stage of development in three different animal models of metastatic breast cancer. |
| Databáze: | OpenAIRE |
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