Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy

Abstract

We have developed a theranostic nanoparticle, ie, cet-PEG-dexSPIONs, by conjugation of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody, cetuximab, to dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) via periodate oxidation. Approximately 31 antibody molecules were conjugated to each nanoparticle. Cet-PEG-dexSPIONs specifically bind to EGFR-expressing tumor cells and enhance image contrast on magnetic resonance imaging. Cet-PEG-dexSPION-treated A431 cells showed significant inhibition of epidermal growth factor-induced EGFR phosphorylation and enhancement of EGFR internalization and degradation. In addition, a significant increase in apoptosis was detected in EGFR-overexpressing cell lines, A431 and 32D/EGFR, after 24 hours of incubation at 37°C with cet-PEG-dexSPIONs compared with cetuximab alone. The antibody-dependent cell-mediated cytotoxicity of cetuximab was observed in cet-PEG-dexSPIONs. The results demonstrated that cet-PEG-dexSPIONs retained the therapeutic effect of cetuximab in addition to having the ability to target and image EGFR-expressing tumors. Cet-PEG-dexSPIONs represent a promising targeted magnetic probe for early detection and treatment of EGFR-expressing tumor cells.

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…Although IONs with conjugated physiological ligands for these receptors have been developed [ 188 , 189 ], humanized antibodies are preferred to avoid activation of the respective signaling pathways without detrimentally impacting the constitutive endocytosis by CME. The most common antibodies for EGFR targeting include cetuximab [ 190 ], nimotuzumab [ 191 ], and single-chain antibody fragments (ScFv) [ 192 ]. In the case of VEGFR targeting, the preferred antibodies include bevacizumab [ 193 ] and anti-VEGF monoclonal antibodies [ 194 ].…”

Radiolabeled theranostics: magnetic and gold nanoparticles

“…72,73 Effective surface conjugation of biocompatible MNPs with Abs, Aps, proteins and enzymes offers the possibility of using these NPs in specific targeting of diseased tissues such as tumors. 74,75 It should be pointed out that the SPIONs with hydrophobic surface can be accumulated within the healthy liver tissue as a consequence of their rapid absorption by macrophages and Kuppfer cells of reticuloendothelial system (RES). Minimized RES assimilation is achieved by conjugating of SPIONs with different biomaterials and hydrophilic polymers (e.g., PEG) that improves their blood half-life and enhanced permeability and retention (EPR) effect and consequently particular accumulation in tumor cell may occur.…”

Injectable Thermo-Sensitive Chitosan Hydrogel Containing CPT-11-Loaded EGFR-Targeted Graphene Oxide and SLP2 shRNA for Localized Drug/Gene Delivery in Glioblastoma Therapy

“…The zeta potential changed to −34.4 ± 0.17 mV for GO-PEG due to the positive charge of N -(aminopropyl polyethyleneglycol)carbamyl-distearoylphosphatidyl-ethanolamine 1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[amino(polyethyleneglycol)] (DSPE-PEG-NH 2 ), indicating the successful PEGylation of GO. The zeta potentials further increased toward the positive side to −19.3 ± 0.64 mV and −11.7 ± 0.82 mV for GO-CET, and GO-CET/CPT11, respectively, indicating the successful conjugation of CET onto GO-PEG owing to the slightly positive charge of CET (isoelectric point = 8.5) and CPT-11 [ 39 ].…”

“…To conjugate CET onto GO-PEG, amine groups on the GO-PEG surface were reacted with activated CET after oxidation of the carbohydrate moieties in CET (an EGFR antibody) to aldehydes [ 39 ]. For this purpose, a 0.1 mg/mL CET solution was prepared in 1 mL ddH 2 O, which was followed by adding 0.2 mL of 0.1 M NaIO 4 dropwise to open the saccharide rings between vicinal diols and leaving two aldehyde groups for spontaneous reaction with the amine groups on GO-PEG.…”