Anti-VCAM-1 and Anti-IL4Rα Aptamer-Conjugated Super Paramagnetic Iron Oxide Nanoparticles for Enhanced Breast Cancer Diagnosis and Therapy

Abstract

The surface protein overexpressed on cancer cells can be used as biomarkers for early detection of specific diseases. Anti-VCAM-1 and anti-IL4Rα DNA aptamers specific to VCAM-1 and IL4Rα receptors that are overexpressed in 4T1 tumor-bearing mice could be used as potential biomarker for both diagnostic and therapeutic applications in cancer biology. Cell Viability and luciferase assay of 4T1-Luc2 cancer cells in the presence of anti-VCAM-1 ssDNA or anti-IL4Rα RNA aptamers was assessed by monitoring the changes in the absorbance and the fluorescence of Alamar blue dye. The aptamer-conjugated SPIO magnetic beads, used for the selective targeting to tumor sites, were monitored using noninvasive MRI and Bioluminescence imaging (BLI). Cell viability and luciferase assays showed that both anti-VCAM-1 and anti-IL4Rα aptamers favor the depletion of cancer cells and limit tumor progression. Microscopic analyses confirmed that the target specific aptamers significantly trigger tumor cell apoptosis and limit cancer cell growth in vitro. The intravenous injection of SPIO nanoparticle-conjugated aptamers were further confirmed using noninvasive MRI and Bioluminescence imaging. Anti-VCAM1 and anti-IL4Rα aptamers, specific to VCAM-1 and IL4Rα receptors overexpressed in 4T1-Luc2 tumor-bearing mice, were used as diagnostic and therapeutic tools.

Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines

“…Already discussed anti-VCAM-1 aptamer conjugated SPIONs, apart from demonstrating favorable tumor imaging ability, were also investigated for tumor growth suppression ( 131 ). When injected along with anti-IL-4Rα aptamer-conjugated SPIONs to tumor bearing mice, these two NMs significantly decreased tumor size comparing to control or single NM-treated animals, indicating that simultaneous functional blockade of these targets potentiates antitumor activity.…”

Mini-Review: Recent Advances in Aptamer Applications

“…Anti-VCAM-1 and anti-IL4Rα DNA aptamers, specific for their cognate receptors overexpressed in 4T1 mammary tumor-bearing mice, were shown by Chinnappan et al 9 to be useful for diagnosis and therapy when conjugated to super paramagnetic iron oxide nanoparticles (SPIONs). Receptor binding by both aptamers triggers tumor cell apoptosis, thus limiting tumor progression in vitro and in vivo.…”

“…Like the use of SPIONs for breast cancer, 9 these magnetic NPs were studied by Fang et al 19 using the known prostate cancer (PC)-specific aptamer, Wy5a, for delivery of Docetaxel (Dtxl), a broad-spectrum anticancer drug. These targeted SPIONs showed controlled drug-release in PC-3 cells in vitro and in vivo, as well as MRI contrastenhancement, plus more efficacious antitumor properties in vivo without systemic toxicity.…”

Interactions of Common Biological Buffers with Iron Oxide Nanoparticles

“…Many studies have also been conducted on the phosphate adsorption capabilities of IONPs for the removal of phosphate contaminants from wastewater systems; however, it should be noted that these studies typically used bare IONPs, where the surfaces are passivated only with hydroxyl groups. − Nevertheless, these studies demonstrate a clear affinity of phosphate ions for the IONP surface. Despite these key findings, the use of PB and PBS for IONP preparations and applications prevails to this day. ,,,− …”

“…Tris is another commonly used biological buffer for IONP applications (Table ), ,,,− despite previous studies, which have demonstrated the ability of the hydroxyl arms of Tris to chelate Fe­(III), as well as the possibility of the amine to participate in complex formation in solution. , Furthermore, a study by Sosa-Acosta et al used Tris as a capping ligand on IONPs and proposed that binding occurs through the hydroxyl groups, leaving the amines free for coupling chemistry. The Tris, however, was added during the co-precipitation synthesis of the IONPs, as opposed to a postsynthesis ligand exchange, so its ability to displace existing ligands was not investigated.…”