**5.1 State-of-the-art approaches of MXenes-based nanobiosensors for cancer biomarkers detection**

Cancer is one of the deadliest diseases worldwide, and acquiring cancer-specific data by quantitative analysis of cancer-associated biomarkers is crucial to monitor cancer progression and for the early treatment [107]. As reported by the World Health Organization, the year of 2030 should be marked by approximately 12 million cancer related deaths, making cancer a major public health problem and one of the most prominent death-causing factors worldwide. The number of new cases of cancer (cancer incidence) is presently around 439 *per* 100,000 *per* capita *per* year [108]. Early-stage diagnostics of various types of cancer diseases is important since it offers opportunities to extend life expectation of patients. Tumor markers exist in tumor cells themselves or are secreted by tumor cells. In either case the presence of these tumor markers above a set threshold may suggest the existence and/or growth of a tumor. The phrase "tumor marker" is often transposed for the term "biomarker" [109] and *vice versa*. Biomarkers can be applied as an early diagnostic tool, to monitor disease progression, as a prognostic tool and as means for prediction and monitoring of clinical response to an intervention.

*According to the National Institute of Health, a biological marker (biomarker): is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.*

A tumor/cancer marker is a substance produced by a tumor or by the host in response to a cancer cell that can be objectively measured and evaluated as an indicator of cancerous processes within the body. The term tumor marker was firstly coined in 1847 and presently there are more than 100 known different tumor markers [110]. Biomarkers have a great potential for screening and diagnostics because they are present in blood and provide information about the health condition [111]. In healthy individuals, the tumor marker concentration is comparatively low level or even absent, while increased values can reveal development and/or progression of a disease [112]. Serum biomarkers providing key information about the disease are important for management of cancer patients since blood aspiration is only a moderately invasive procedure. There is clear need for early-stage cancer diagnostics, efficient treatment and posttreatment monitoring to avoid progress of the disease into advanced stages. Therefore there is an enormous demand for efficient less-invasive investigation *i.e.* analysis of cancer biomarkers in plasma/ serum samples at low limit of detection [113].

a conductive support for immobilization of aptamer probes. Wang *et al*. modified electrode surface with MXene for development of a MUC1 biosensor [117]. The ferrocene-labeled complementary DNA was bound onto MXene nanosheets to design a detection probe for electrochemical signal amplification. GCE was modified by electrodeposited AuNPs with MUC1 aptamer attached to the modified electrode *via* Au-S bonds. The modified electrode was blocked using bovine serum albumin (BSA) in order to resist non-specific interactions. Next, a detection probe was attached to the modified electrode *via* hybridization between complementary DNA and a MUC1 aptamer. Upon interaction of MUC1 with such an electrode, the detection probe was detached from the working electrode resulting in a decrease of an electrochemical signal (a signal-off response). This competitive aptasensor detected MUC1 with LOD of 0.33 pM with a linear range up to 10 mM. The relative standard deviation (RSD) of the peak current difference response was 1.43%, indicating that the aptasensor had good reproducibility. The peak current difference response of the aptasensor did not change much in ten days, indicating its accept-

*Ti3C2 MXene-Based Nanobiosensors for Detection of Cancer Biomarkers*

*DOI: http://dx.doi.org/10.5772/intechopen.94309*

*Currently, there are more than 20 known types of mucins. They are encoded by MUC genes and represent high molecular weight glycoproteins expressed on epithelial cells. Aberrantly glycosylated mucins are expressed in*

*MicroRNAs (miRNAs) overexpression is a biomarker for a number of diseases including cardiovascular disorders, cancer, rheumatic diseases, diabetes, neurological disorders, liver diseases, kidney diseases, and immune dysfunction. The microRNAs (miRNAs) are biomolecules composed of 18–24 nucleotides and they play a key role in biological processes such as cell proliferation, apoptosis and tumorigenesis. Abnormal expression has been monitored in breast cancer as well as in other cancer types with observed blood stability. The miRNA-182 demonstrates tissue specificity and sequential expression in the different stages during lung*

The label-free strategy for the ultrasensitive detection of miRNA-182 was based on glassy carbon electrode (GCE) modified step-by-step by van der Waals forces and electrostatic interactions with MoS2/Ti3C2, AuNPs, ssRNA [118]. BSA was used to block unbound gold particles surface and avoid nonspecific adsorption. The biosensor was able to determine miRNA-182 with LOD of 0.43 fM (a linear range of 1 fM - 0.1 nM) by DPV method [118]. The recovery was 105%, 95.3% and 93.0% for the concentration of 10<sup>10</sup> M, 10<sup>12</sup> M and 10<sup>14</sup> M of the analyte respectively,

Duan with co-workers [119] developed an impedimetric aptasensing strategy based on a novel zero dimensional (0D)/2D nanohybrid of Ti3C2Tx nanosheets decorated with FePc QDs (denoted as Ti3C2Tx@using iron phthalocyanine quantum dots (FePcQDs)) for miRNA-155 detection. The miRNA-155 was established by applying impedimetric aptasensor with LOD of 4.3 aM (S/N = 3, a linear concentration range from 0.01 fM to 10 pM). The observed relative standard deviation (RSD) of the five aptasensors for detection of miRNA-155 was as low as 2.98**%**, demonstrating good reproducibility of the proposed aptasensor. Moreover, the signal remained 104**%** of the original signal after 15 days of storage, revealing a

Multiple (miRNA-21 and miRNA-141) and rapid (80 min) analysis of onco microRNAs in total plasma was carried out with combination of AuNPs (5 nm) decorated MXene as an electrode interface and a duplex-specific nuclease (DSN) as an amplification system applied onto home-made screen-printed gold electrode

*cancer development or evolution. The miRNA-155 is overexpressed in human breast cancers.*

manifesting its effective detection of miRNA-182 in real sample [118].

satisfactory stability of the present aptasensor [119].

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able stability [117].

*cancer cells and serve as oncogenic molecules.*

*Limit of Detection (LOD): the level of analyte that leads to a sensor signal which is statistically significantly different from the background signal obtained in the absence of the analyte. A frequently used definition of LOD is a concentration that gives a signal greater than three times the standard deviation of a blank sample consisting entirely of a matrix (S/N) = 3*.

The unique physico-chemical properties of MXenes make them a significant tool that can be employed in the cancer therapy (photothermal therapy, photodynamic therapy, radiation therapy, chemotherapy), cancer imaging (CT/MRI/PA imaging) as well as cancer theranostic applications [21].
