Highly Sensitive Electrochemical Sensor for Anticancer Drug by a Zirconia Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite.

Manthrapudi Venu,Yenugu Veera Manohara Reddy,Vinod Kumar Gupta,Sada Venkateswarlu,Minyoung Yoon,Gajulapalli Madhavi,Ankireddy Seshadri Reddy

doi:10.1021/acsomega.8b02129

Abstract

Because of their large surface area and conductivity, some inorganic materials have emerged as good candidates for the trace-level detection of pharmaceutical drugs. In the present work, we demonstrate the detection of an anticancer drug (regorafenib, REG) by using an electrochemical sensor based on a nanocomposite material. We synthesized a zirconia-nanoparticle-decorated reduced graphene oxide composite (ZrO2/rGO) using a one-pot hydrothermal method. Reduction of the graphene oxide supports of the Zr2+ ions with hydrazine hydrate helped in preventing the agglomeration of the zirconia nanoparticles and in obtaining an excellent electrocatalytic response of the nanostructure ZrO2/rGO-based electrochemical sensor. Structural and morphological characterization of the nanostructure ZrO2/rGO was performed using various analytical methods. A novel regorafenib (REG) electrochemical sensor was fabricated by immobilizing the as-prepared nanostructure ZrO2/rGO on to a glassy carbon electrode (GCE). The resulting ZrO2/rGO/GCE could be used for the rapid and selective determination of REG in the presence of ascorbic acid and uric acid. The ZrO2/rGO/GCE showed a linear response for the REG analysis in the dynamic range 11–343 nM, with a remarkable lower detection limit and limit of quantifications of 17 and 59 nM, respectively. The newly developed sensor was used for the accurate determination of REG in both serum samples and pharmaceutical formulations, with satisfactory results.

Highlights

Regorafenib [4-(4-(3-(4-chloro-3-(trifluromethyl) phenyl)-3flurophenoxy)-N-ethylpicolinamide] (BAY 73-4506) is an orally bioavailable multikinase inhibitor (MKI), which obstructs multiple tumor pathways, inhibiting targets in the receptors of the vascular endothelial growth factor 1−3 (VEGF 1−3), fibroblast growth factor, and platelet-derived growth factor, including the mutant oncogenic kinesis c-KIT, RET, and B-RAF.[1,2] This MKI generates dynamic metabolites, which could become agglomerated, in elderly, malnourished patients or in patients treated for hepatocellular carcinoma, as in the case of other MKIs.[3]
Pristine ZrO2 nanoparticles (Figure 1a) are nearly spherical with a uniform size of size of 6−9 nm, which is in good agreement with the calculated values based on the powder X-ray diffraction (PXRD) result
The selected area electron diffraction (SAED) patterns for ZrO2 (Figure 1c) and the ZrO2/reduced graphene oxide (rGO) nanocomposite shown in Figure 1f illustrate the crystalline dots instead of amorphous rings, which indicate the polycrystalline nature of the ZrO2 nanoparticles and nanocomposite

Summary

Introduction

Regorafenib [4-(4-(3-(4-chloro-3-(trifluromethyl) phenyl)-3flurophenoxy)-N-ethylpicolinamide] (BAY 73-4506) is an orally bioavailable multikinase inhibitor (MKI), which obstructs multiple tumor pathways, inhibiting targets in the receptors of the vascular endothelial growth factor 1−3 (VEGF 1−3), fibroblast growth factor, and platelet-derived growth factor, including the mutant oncogenic kinesis c-KIT, RET, and B-RAF.[1,2] This MKI generates dynamic metabolites, which could become agglomerated, in elderly, malnourished patients or in patients treated for hepatocellular carcinoma, as in the case of other MKIs.[3]. It is important to maintain the benefits of these treatments, in the elderly or in patients treated for metastatic colon cancer and gastrointestinal tumors, which is approved by FDA.[6−11] The most serious adverse reaction was drug-induced hepatotoxicity, and a black box warning has been indicated by the US-FDA.[12] the detection of this anticancer active drug is extensively important and a universal challenge. Some of the sophisticated analytical methods such as high-performance liquid chromatography (HPLC),[13] liquid chromatography-mass spectrometry (LC-MS),[14−19] and spectrophotometry[20] are used for the detection of REG in urine, plasma, and other biological samples.

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Conclusion