Improving sensitivity and specificity of capturing and detecting targeted cancer cells with anti-biofouling polymer coated magnetic iron oxide nanoparticles

Abstract

Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7 ± 6.4%) when separating 100 targeted tumor cells from 1×105 non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1 mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads®).

Going even smaller: Engineering sub‐5 nm nanoparticles for improved delivery, biocompatibility, and functionality

“…Another advantage of smaller nanoparticles with higher surface-to-volume ratios is their capacity for the higher surface ligand density. When surface/volume ratio increases, the number of active sites is increased, suggesting that, by using smaller IONPs (<5 nm diameter) to carry ligands, the process could become more efficient (Lin et al, 2017). As ligand-mediated active, targeting to biomarkers by nanoparticles is dependent on the binding between targeting ligands on the surfaces of nanoparticles and targeted tissue or cell surface biomarkers, bearing more ligands on the unit surface area may increase the probability of targeting ligands interacting with the targeted biomarker, thus enhancing targeting efficiency and affinity of nanoparticles to the biomarkers.…”

Impact of nanoparticles on neuron biology: current research trends

“…3,[39][40][41][42][43] To get better therapeutic results, various types of nanoparticles have been studied in neurons, and among those, carbon-based nanoparticles are mostly reported, 4,[44][45][46][47][48] followed by gold and silver nanoparticles (AgNPs). [49][50][51] Despite having many beneficial properties, nanoparticle also raises few health hazard and toxicity issues. To better understand the safety profile of the nanoparticles, several attempts have been made to know whether nanoparticles cause any side effects or toxic effects.…”

Magnetic Nanoparticles: From Design and Synthesis to Real World Applications

“…Subsequently, target cells are resuspended and removed (step 4). (Reproduced with permission from [ 202 ]); ( B ) Enzymatic transformation of magnetic particles for selective sorting of cancer cells (reproduced with permission from [ 198 ]). ALPP: placental alkaline phosphatase.…”