Sensing And Detection Of Tumor Markers Based On Platinum Group Metal Nanomaterials With Electrooxidation Activity

Malignant tumor is much harmful to human beings.When there are tumor cells in human body,tumor markers would be generated by tumor cells or released by the body.Therefore,it is necessary to explore an effective and convenient method to detect tumor markers for the preoperative prevention and postoperative treatment of malignant tumors.Electrochemical sensors have attracted much attention because of their advantages of sensitivity and simple operation.However,electroactive probes of electrochemical sensors are faced with the problems of signals being easily disturbed,insufficient signal strength,inaccurate detection,single detection signal and low efficiency.It is particularly significant to develop new electroactive probes with excellent performance and improve the electrochemical signals of electroactive probes.Among many materials,platinum group metal（PGM）nanocomposites with high electronic density of states have been extensively researched in the field of electrochemistry.Because the d-band center of PGM can be declined by compounding with other materials,which provides excellent electronic environment for the reaction system.However,most of these reports focused on the study of PGM nanocomposites as electrochemical catalysts to promote reaction,ignoring the electrochemical activity of PGM nanocomposites themselves.In addition,the nanomaterials prepared by the combination of PGM and plasmon materials have excellent characteristics of plasmon-enhanced optical signals.Whether this plasmon-enhanced effect could be applied to amplify the electrochemical signals is meaningful to broaden the application of PGM nanocomposites in the field of electrochemical analysis.In order to solve the problems faced by electroactive probes,different PGM nanocomposites were prepared,and their electrochemical oxidation activity was explored in this paper.Based on theplasmon-enhanced electrooxidation activity of PGM nanocomposites,sensors were designed to achieve the sensitive,accurate and multi-signals detection of tumor markers.The main contents of this paper are listed as follows:1.In order to solve the problem that the signal of electroactive probe on the electrochemical interface is easily disturbed and the intensity is not ambitious enough,Au Ru nanoparticles（NPs）with plasmon-enhanced electrooxidation activity were designed as the probe.Because Au Ru NPs could harvest light energy through local surface plasmon resonance（LSPR）,and achieve the separation of holes and electrons.Then the electrons flowed into the external circuit,and the generated holes accelerated the electrochemical oxidation process of Ru⁰,amplifying the electrochemical oxidation signal at the potential of0.78 V.Subsequently aptamers modified Au Ru NP-Au NP dimers were assembled and used as probes to construct electrochemical sensor.Under illumination,Au Ru NP-Au NP dimers produced intense electromagnetic field through the plasmonic coupling between Au Ru NPs and Au NPs,which further enhanced the electrooxidation activity and improved the anti-interference performance of the sensor.Finally,the sensitive determination of human epidermal growth factor receptor-2（HER2）was achieved.The linear range of the sensor was10 pg/m L-100 ng/m L,and this sensor could be used to detect HER2 in the serum of positive patients.2.On the basis of improving the anti-interference and intensity of signals through plasmon-enhanced electrooxidation activity,the electrooxidation signals of Au Pt NPs were used as new detection signals.At the same time,in order to further improve the accuracy of electrochemical detection,Co-MOF/Fe₃O₄/Ag nanosheets（NSs）were introduced as reference beacons.It was found that the electrooxidation peak of Au Pt NPs belonged to Pt⁰ at the potential around-0.7 V,and Au Pt NPs also had the characteristic of plasmom-enhanced electrooxidation activity like Au Ru NPs.Therefore,when Au Pt NPs were used as detection probes,the anti-interference performance and detection signal intensity would be improved.On the other hand,the electrochemical oxidation signals of Co-MOF/Fe3O4/Ag NSs were identified as reference signals,their signals would not change with the concentration of tumor markers,which enhanced the reproducibility of signals.When concentration range of epithelial cell adhesion molecule（EpCAM）was 100 pg/m L to 100 ng/m L,the ratio signal of the sensor decreased linearly with the increase of the logarithm of EpCAM concentration.So the designed electrochemical ratio sensor achieved the accurate determination of EpCAM.In addition,this sensor was also suitable for the determination of EpCAM in serum.3.Detection of dual tumor markers could get more accurate and effective information about cancer and improve the success rate of diagnosis.Therefore,two electrochemical detection probes with strong signal strength and non-interference were developed.AgRu NPs and Ag Pt NPs with the most excellent electrooxidation activity were prepared by optimizing the synthesis conditions.Then,based on the fact that the electrooxidation peaks of Ru⁰ and Pt⁰in PGM nanocomposites could not interfere with each other（their peak positions are around0.8 V and-0.7 V,respectively）,an electrochemical sensor for parallel detection of HER2 and EpCAM was constructed.It was different from using single signal to detect tumor markers in the past,the double electrochemical signals of AgRu NPs and Ag Pt NPs were employed for determination of multiple tumor markers,could increase the diagnosis success rate of malignant tumors.In addition,the introduction of Ag as plasmon material not only enhanced the conductivity of PGM nanocomposites,but also could collect light energy through LSPR,which promoted the electrooxidation of 0 valent PGM.That lead to PGM nanocomposites being provided with stronger electrochemical signal.The linear ranges of HER2 and EpCAM were 1 pg/m L-100 pg/m L and 1 pg/m L-500 pg/m L,respectively.And this developed sensor could be used to detect HER2 and EpCAM in serum.