The role of nanomaterials on the cancer cells sensing based on folate receptor: Analytical approach
Graphical abstract
Introduction
Cancer is an abnormal cell growth that could then spread neighboring organs or tissues. Despite advances in cancer detection devices, cancer remains the second main cause of mortality around the world. According to World Health Organization (WHO) reports, in 2007, 7.9 and in 2018, 9.6 million people passed away from cancer and it is estimated that this number will increase to 12 million deaths in 2030. The cost of cancer diagnosis and therapy was US$1.16 trillion in 2010 [1]. In men, lung, stomach, prostate, liver and colorectal are the most frequent cancers, however, in women, breast, colorectal, lung, cervix and thyroid are the common cancers.
Early stage detection of cancers is the substantial problem in cancer therapy and about 30–50% of cancers could be prevented by control of risk factors and doing of some evidence-based tactics [1]. After the diagnosis of cancer, controlling of the cancer is very crucial which is deeply dependent on the clinical test results and the doctors’ prescriptions. Conventionally, different techniques have been established for the detection of cancers including photon emission computed tomography (PECT) [2], immunohistochemistry [3,4], polymerase chain reaction (PCR) [5], single-positron emission tomography (SPET) [6], magnetic resonance imaging (MRI) [7] and flow cytometry [8]. Currently, these techniques are broadly employed in cancer detection. However, most of these techniques suffer from some limitations such as high cost, long time of analysis, false-positive/negative results, low-sensitivity and also usually provide qualitative results [9,10].
Due to the aforementioned disadvantages of the currently used techniques, fabrication of the new analytical methods with simple, low-cost, rapid, accurate and specific features are of great importance in clinical diagnosis of cancer, providing the diagnosis of cancer even without referring to the clinics. Currently, main analytical methods for the detection of tumor cells are electrochemical [[11], [12], [13]], optical [14] and quartz crystal microbalance (QCM) [15] based sensors. These techniques were applied with different strategies such as labeled/label free, antigen/antibody conjugation, DNA complementary segments, protein conjugates and membrane receptors to develop aptamers, immunosensors, enzyme and other molecule/biomolecule based biosensors. However, the target specific approaches are considered as ideal methods for sensors’ construction which mainly provided with antigen/antibody interactions, DNA complementary segments, protein conjugates (streptavidin/biotin) and membrane receptors [16]. One of the targeted cell sensing method is using the folate receptor (FR) and folic acid (FA) interactions. FRs, alpha and beta, are overexpressed on the membrane of the most of the cancer cells (not normal cells) [17,18]. FA molecules are uptake by cells using various transportation systems including FRs, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) [17]. Currently, monoclonal antibodies and FA binding are used for the detection of FR-positive cells. FR is a fascinating agent for various medical targeted therapy [[19], [20], [21], [22]] and imaging [[23], [24], [25], [26], [27]] of cancer cells because of the high affinity between FR and FA with dissociation constant (Kd) of about 0.1–1 nM. FR based sensing methods possess some prominent advantages over other targeted methods; 1) the functionalization of the materials with FA for sensitization to FRs is simple and low-cost; 2) the synthesized materials could be stored at room temperature or refrigerator without any severe care conditions and 3) the primary materials to construct the cytosensing probe are purely accessible. Therefore, not only construction of FR based cytosensors is facile but also provide protocols with high sensitivity and specificity towards the detection of different cancer cells.
To date, different review papers were published to explain the applications of FR in targeted drug delivery [[28], [29], [30]], gene delivery [31], imaging [[32], [33], [34]] and diagnosis [35]. However, the quantitative sensing of the cancer cells using FR was not reported yet. The general mechanism of action of the FR/FA interactions for various aims is represented in Scheme 1. This review is intended to report the FR-based detection of cancer cells published from 2010 to 2019. In this review, we emphasis on the recent advancements in FR-based cytosensing of the FR-overexpressed tumoral cancer cells to show their possibilities and advantages. This review was categorized under five main sections based on the advanced materials used to the fabrication of the cytosensor including gold nanoparticles, carbon, magnetic and porous, polymers and other types of materials for the detection cancer cells. Analytical figures of merit and some important features of the reported approaches are collected in Table 1. Each section reports the details of the construction of the cytosensors and evaluates the advantages and analytical figures of merit of the reported cytosensors.
Also, applications of FR/FA interactions for imaging of FR-overexpressed cancer cells were discussed in “section 3”. However, this application was already reviewed by different authors such as Pirsaheb et al. [36], Fernández et al. [37] and Ledermann et al. [38].
Section snippets
Gold nanoparticles (AuNPs) based cytosensors
AuNPs are regarded as one of the most preferred nanoparticles for the developments of sensing probes because of their superior physico-chemical properties [39]. These properties lead to the construction of sensitive, stable and biocompatible biosensors. In this section, advances in applications of AuNPs in FA/FR based cytosensing were presented to provide a brief of the reported strategies for the detection of FR-overexpressed cancer cells.
Bioimaging of cancer cells
Determination of the tumor site is the first step in cancer diagnosis and then therapy. Therefore, fabricating of efficient approaches for selective and precise targeting of tumoral cancer cells has high importance in clinics. For this aim, fluorescence imaging based methods play main role in the imaging of cancers because of some attracted features of high sensitivity and spectral efficiency.
Carbon based fluorescent materials attracted attentions due to their low toxicity, high
Conclusions and future prospects
In conclusion, the contribution of materials (especially nanomaterials) in the construction of cytosensors based on the FA/FR interactions was reviewed. FRs are overexpressed about in all cancer cells, enabling to the selective detection of the cancer cells. FR-based recognition of cancer cells essentially relies on binding of FA-functionalized nanomaterials with FR of the cancer cells which governs the specificity of FR-based sensing platforms. Due to the exceptional and fascinating properties
Acknowledgments
The authors would like to acknowledge the financial supports from Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences as PhD thesis of J. Soleymani (registration no: 59166).
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