Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF) for targeting brain tumors

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with recombinant human epidermal growth factor (SPION–EGF) were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION–EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION–EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION–EGF conjugates in animals provided receptor-mediated targeted delivery across the blood–brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs ( P <0.001). SPION–EGF conjugates provide targeted delivery and efficient magnetic resonance contrast enhancement of EGFR-overexpressing C6 gliomas.

Nanoparticles for brain-specific drug and genetic material delivery, imaging and diagnosis

“…In addition, as has been described with other nanoparticles, the binding affinity of SPIOs can be modified by binding different molecules to their structure to produce nanoparticles with increased BBB crossing ability, targeting abilities (ligand-receptor mediated or other biomarkers) and fluorescent properties for optical imaging. Selective targeting of SPIO nanoparticles has been achieved by combining a SPIO with human recombinant EGF, leading to high intracellular incorporation in C6 glioblastoma cells [92]. SPION conjugated with cetuximab allowed binding and internalization into glioblastoma cells [93].…”

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

“…47 Liu et al also found that C225-USPIO has potential use as an MRI contrast agent to noninvasively detect early-stage nasopharyngeal carcinoma with EGFR overexpression. 48 Furthermore, Shevtsov et al 49 studied SPION conjugated with recombinant human epidermal growth factor (SPION-EGF) as a potential agent for MRI contrast enhancement in malignant brain tumors. They first analyzed the interaction of SPION-EGF conjugates with cells in a C6 glioma cell culture.…”

“…Collectively, this work shows that SPION can be successfully used for targeted delivery and subsequent efficient MR contrast enhancement of C6 gliomas with EGFR overexpression. 49 A clinically relevant target in cancer work is the tyrosine kinase Her-2/neu receptor, which has a significant role in staging and curing breast cancer. Artemov et al 50 imaged Her-2/neu receptors in a panel of breast cancer cells with differential cell membrane receptor expression.…”

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using&nbsp;noninvasive molecular magnetic resonance&nbsp;imaging

“…17,24,[26][27][28][48][49][50] In this study, USPIO was conjugated with antibodies for the recognition of CD133, a surface marker associated with colorectal cancer and brain tumors, among other cancers, to produce a novel targeted contrast agent for detecting CSCs in vivo. Observed from transmission electron microscopy, the mean core diameter of whole particles was 29±7.9 nm, which assured efficient targeting and optical imaging of tumors in vitro and in vivo (Figure 1).…”

“…61 Similar to other studies, our data demonstrated that USPIO-CD133 Ab displayed good biocompatibility and no significant cytotoxicity in tumor cells and in animals, suggesting that USPIO-CD133 can specifically and safely label CD133-positive cells in vitro and in vivo. 50,62 The potential for intravenous nanoparticles targeting brain tumors has been actively debated, due to the bloodbrain barrier and nonspecific uptake of particles by the endothelial system. However, it has been shown that the vascular structure in brain tumors is significantly different and is characterized by increased permeability.…”