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.
Highlights
Imaging is critical for management of patients with breast cancer including diagnosis, treatment planning and response assessments
We show that the combination of two different ligands on the nanochain particle effectively captures the dynamic nature of breast cancers and targets the spatial and temporal variations in receptor presentation on the tumor endothelium
In order to prevent the aggregation of iron oxide nanoparticles, 340 mg of Imaging breast cancer using a dual-ligand nanochain particle anhydrous citric acid was added to the particle solution and the pH was consequentially increased to 5.2 using ammonia
Summary
Imaging is critical for management of patients with breast cancer including diagnosis, treatment planning and response assessments. Various targeting schemes have been employed to direct nanoparticle imaging agents to cancers [1, 2]. Traditional targeting strategies decorate the surface of nanoparticles with a ligand directing them to upregulated receptors on breast cancer cells within the tumor interstitium. Rather than targeting the tumor interstitium, an alternative strategy is to use vascular targeting and direct the nanoparticles to the altered endothelium associated with breast cancer.
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