Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles

Abstract

We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 x 10(9) per HeLa cell, when the co-culture concentration was 40 microg Fe mL(-1) or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages.

Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy

“…The technical details and performances of our transmission x-ray microscope were reported [37,38,45]. The field of view is 24 μm and the detector is a 2048 × 2048 CCD.…”

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

“…Nanomaterials have been used as radio-sensitizers for cancer treatment, with minimal side effects [123][124][125]. Metal-based nanomaterials can generate photoelectrons to enhance the dose effect of RT and induce cytotoxicity in tumor cells through increased ROS production [123][124][125].…”

“…Nanomaterials have been used as radio-sensitizers for cancer treatment, with minimal side effects [123][124][125]. Metal-based nanomaterials can generate photoelectrons to enhance the dose effect of RT and induce cytotoxicity in tumor cells through increased ROS production [123][124][125]. In a recent study, Wu et al showed that the combination of RT and a magnetic nanoparticle-based platform with cationic polymer modification induced cytotoxicity in glioma cells and increased the median survival of immunocompetent and athymic glioma mice [126].…”

Optimising element choice for nanoparticle radiosensitisers

“…Despite this, it remains an open question as to whether gold is the optimum material for this purpose. Only a handful of other elements have been investigated for use as radiosensitisers (including platinum, hafnium, gadolinium, and iron (12)(13)(14)(15)(16) ), and there have been no systematic experimental or theoretical comparisons between different materials.…”