Role of Surface Chemistry in Mediating the Uptake of Ultrasmall Iron Oxide Nanoparticles by Cancer Cells

Abstract

Ultrasmall iron oxide nanoparticles (USIONPs) (<4 nm) have recently attracted significant attention because of their potential as positive T 1 magnetic resonance imaging (MRI) contrast agent contrary to larger superparamagnetic iron oxide nanoparticles (>6 nm) which act as negative T 2 MRI contrast agents. However, studies on the cellular uptake behavior of these nanoparticles are very limited compared to their counterpart, larger-sized superparamagnetic iron oxide nanoparticles. In particular, the effects of specific nanoparticle parameters on the cellular uptake behavior of USIONPs by various cancer cells are not available. Here, we specifically investigated the role of USIONPs’ surface functionalities [tannic acid (TA) and quinic acid (QA)] in mediating cellular uptake behavior of cancer cells pertaining to primary (U87 cells) and metastatic (MDA-MB-231Br cells) brain malignancies. Here, we chose TA and QA as representative capping molecules, wherein TA coating provides a general negatively charged nontargeting surface while QA provides a tumor-targeting surface as QA and its derivatives are known to interact with selectin receptors expressed on tumor cells and tumor endothelium. We observed differential cellular uptake in the case of TA- and QA-coated USIONPs by cancer cells. Both the cell types showed significantly higher cellular uptake of QA-coated USIONPs compared to TA-coated USIONPs at 4, 24, and 72 h. Blocking studies indicated that P-selectin cell surface receptors, in part, mediated the cellular uptake of QA-coated USIONPs. Given that P-selectin is overexpressed in cancer cells, tumor microenvironment, and at the metastatic niche, QA-coated USIONPs hold potential to be utilized as a platform for tumor-targeted drug delivery and in imaging and detection of primary and metastatic tumors.

Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications

“…The result revealed that these cancer cells selectively uptaked QA-USION, which was partially mediated by p-selectin. 75…”

Targeting Selectins Mediated Biological Activities With Multivalent Probes

“…Recently, ultrasmall iron oxide nanoparticles (USIONPs) of size <4 nm were used as a positive T1 relaxivity MRI contrast agent, as they offer bright MRI imaging and high-resolution, resulting in easy detection of the target (Liu et al, 2019). Recently, Rao et al reported the synthesis of quinic acid (QA)-coated USIONPs to target P-selectin overexpressed aggressive cancer cells (Narkhede et al, 2019).…”

“…Recently, ultrasmall iron oxide nanoparticles (USIONPs) of size <4 nm were used as a positive T1 relaxivity MRI contrast agent, as they offer bright MRI imaging and high-resolution, resulting in easy detection of the target ( Liu et al, 2019 ). Recently, Rao et al reported the synthesis of quinic acid (QA)-coated USIONPs to target P-selectin overexpressed aggressive cancer cells ( Narkhede et al, 2019 ). Working under the same notion, Liu et al reported the synthesis of USIONPs-PEG-SLex nanoparticles to assess in vivo E-selectin expression level in nasopharyngeal carcinoma (NPC) metastasis ( Liu et al, 2019 ).…”

Background Signal-Free Magnetic Bioassay for Food-Borne Pathogen and Residue of Veterinary Drug via Mn(VII)/Mn(II) Interconversion

“…Intensive efforts have been made to improve the analytical performance of conventional MNP-implemented MRS sensors. We and other researchers have used different strategies to improve the sensitivity and stability of conventional MRS biosensors, but they are still not competent to detect small molecules with facile operation. ,, Alternatively, we have resorted to paramagnetic ion-mediated MRS sensors where the valence state change of paramagnetic ions such as Fe 3+ and Cu 2+ can result in a significant change in the T 1 / T 2 signal of NMR. , For example, we have reported the difference in T 1 values of water protons between Fe 2+ and Fe 3+ aqueous solutions and developed a range of assays using their interconversion. Compared with MNPs, the use of paramagnetic ions have two advantages: (i) It is much easier to prepare the aqueous solution of paramagnetic ions than that of MNPs and the paramagnetic ion solution generally has a longer shelf life and (ii) paramagnetic ions have different valence states that can be interconverted by redox reactions, providing a versatile magnetic sensing platform.…”

“…We and other researchers have used different strategies to improve the sensitivity and stability of conventional MRS biosensors, but they are still not competent to detect small molecules with facile operation. 13,17,18 Alternatively, we have resorted to paramagnetic ion-mediated MRS sensors where the valence state change of paramagnetic ions such as Fe 3+ and Cu 2+ can result in a significant change in the T 1 /T 2 signal of NMR. 19,20 For example, we have reported the difference in T 1 values of water protons between Fe 2+ and Fe 3+ aqueous solutions and developed a range of assays using their interconversion.…”