Advances in prostate specific antigen biosensors-impact of nanotechnology

doi:10.1016/j.cca.2020.01.028

Clinica Chimica Acta

Volume 504, May 2020, Pages 43-55

https://doi.org/10.1016/j.cca.2020.01.028 Get rights and content

Highlights

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A variety of biosensors for prostate-specific antigen were investigated.
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Three categories of aptasensors, peptisensors and immunosensors were envisaged.
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These biosensors were electrochemical, electrochemiluminescence, fluorescence or SERS.
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Sensitivity of most of these biosensors was enhanced using nanomaterials.

Abstract

Prostate cancer is one of the most dangerous and deadly cancers in elderly men. Early diagnosis using prostate-specific antigen (PSA) facilitates disease detection, management and treatment. Biosensors have recently been used as sensitive, selective, inexpensive and rapid diagnostic tools for PSA detection. In this review, a variety of PSA biosensors such as aptasensors, peptisensors and immunesensors are highlighted. These use aptamers, peptides and antibodies in the biorecognition element, respectively, and can detect PSA with very high sensitivity via electrochemical, electrochemiluminescence, fluorescence and surface-enhanced Raman spectroscopy. To improve the sensitivity of most of these PSA biosensors, different nanostructured materials have played a critical role.

Introduction

Prostate cancer, as one of the most common diseases, is considered as a major cause of death in men [1], [2]. Prostate-specific antigen (PSA), a serine protease, is the most important, reliable and preferred biomarker for early diagnosis of prostate cancer [3], [4]. PSA is secreted from normal prostate glandular cells and prostate cancer cells [5]. This glycoprotein biomarker (33–34 KDa) is also known as kallikrein-3 and can be used for evaluating healthy individuals or patients wherein normal serum concentration should be lower than 4 ng mL⁻¹ (cutoff value) in men. When prostate cancer occurs, this biomarker increases in serum. In addition to prostate cancerous cells, this biomarker also increases in breast cancer (with a median level of 0.31 ng mL⁻¹). Early detection of prostate cancer through clinical and novel bioanalysis platforms will impact survival. Therefore, finding improved diagnostic tools with high selectivity, sensitivity and stability is necessary. Up to now, several antibody-based methods such as radioimmunoassay [6], enzyme-linked immunosorbent assay (ELISA) [7], surface plasmon resonance (SPR) immunoassay [8] and fluorescence immunoassay [9] have been used for detection of this biomarker. The most important limitations of these methods include high cost, complicated technology, limitations of laboratory tests, lack of portable devices and role of interfering factors. On the other hand, biosensors are designed and produced with lower costs and can detect appropriate analytes with high sensitivity and specificity [3], [10].

An increased ratio of surface area to volume and introducing special physicochemical properties including higher (re)activity and quantum behaviors have led to huge applications of nanostructured materials in design of the biosensor transducers. Nanostructured materials (i) increase the surface area of the transducer leading to higher surface concentration of the biorecognition element; (ii) provide more successful and stable immobilization of the biorecognition element on the transducer surface [11], [12]; (iii) participate in the detection process through conjugation with the biorecognition element [13], [14]; (iv) change the way to generate the output signal [15], [16]; (v) represent synergism effects (e.g. when employed as nanocomposites); (vi) are employed as tags or labels [14], [17], [18]; and (vii) provide multiple analyte detection [19]. These factors lead to amplified signals generation followed by an increment in sensitivity and selectivity [20], [21].

The biosensors have hitherto been reported for the detection of PSA and are categorized as aptamer- (aptasensors), peptide- (peptisensors) and antibody-based (immunosensors) biosensors. Based on the type of biorecognition element, the PSA biosensors are discussed in the following part. The main details of each designed biosensor are also provided in several tables. The results of this review may be considered to define new related researches, applicable for the production of commercial PSA diagnosis devices and also can provide optimized experimental procedures for early diagnosis of prostate cancer.

Section snippets

PSA aptasensors

For diagnosis, aptamers have several advantages over antibodies such as in vitro production, smaller size, reversible conformation against temperature changes, non-immunogenicity, functionalization capability, and stability [22], [23]. The systematic evolution of the ligands by exponential enrichment (SELEX) process was followed toward the glycosylation site of the glycoprotein as a case of PSA and an important sign for cancer growth [24]. Here, a PSA aptamer was electrochemically used in a

PSA peptisensors

Peptides are naturally or artificially synthesized through the polymerization of amino acids by desired peptide bonds between the carboxyl groups [57]. Fast and low-cost production, easy functionalization, high stability and the same genus against most of the disease biomarkers are some of the advantages of peptide sequences application in biosensors fabrication [58], [59]. We have introduced the term “peptisensor” for peptide-based biosensors for the first time [60]. In all of the peptide

PSA immunosensors

Although antibodies have similar constructional features, they show a wide variety and significant differences in their binding regions against antigens [71], [72]. Because of the high specificity and affinity, antibodies are considered as ideal biological diagnostic elements. An electrochemical PSA immunosensor was designed based on molecularly imprinted polymer (MIP) and a nanocomposite containing Fe₃O₄ nanoparticles, graphene oxide, multi-walled carbon nanotube and a PSA antibody [73].

Other PSA biosensors

In addition to the previous discussed PSA biosensors, those which were based on aptamer, peptide or antibody, several PSA biosensors have been introduced so far that employed other materials as biorecognition elements. Our research team designed an electrochemical biomimetic PSA biosensor based on a molecularly imprinted polymer [169]. In this biosensor, a thin film of polypyrrole was electropolymerized as an artificial antibody. In this study, the transducer was a gold screen-printed electrode

Conclusion

Given that the early diagnosis of prostate cancer is very important, various types of PSA biosensors were investigated in three main categories of aptasensors, peptisensors and immunosensors. Immunosensors have the disadvantages of time-consuming and expensive production, temperature sensitive and limited functionalization of the antibodies, and immunogenicity effects. In the aptasensors, rapid degradation by nucleases, renal filtration from bloodstream, interaction with some intracellular

Perspectives

Functionalizing biodegradable components with materials that can form more stable bonds with the transducer as well as utilizing more efficient biorecognition elements in the structure of PSA biosensors can be one of outline of the future researches. It seems that the use of nanostructures as signal transducers, and biorecognition elements with high affinity, stability and specificity to bind PSA can propel the biosensors to higher sensitive diagnostic tools. Nanostructures with higher

Acknowledgments

We would like to thank the Research Council of Shiraz University of Medical Sciences (20907) for supporting this research.

References (170)

H. Grönberg
Lancet
(2003)
C. Cao et al.
Biosens. Bioelectron.
(2006)
G. Tondro et al.
Sens. Actuators, B
(2018)
L. Yang et al.
Adv. Drug Deliv. Rev.
(2011)
H. Heli et al.
Anal. Biochem.
(2009)
N. Sattarahmady et al.
Biosens. Bioelectron.
(2010)
Y. Li et al.
Gold Bull.
(2010)
Y.-Y. Lin et al.
Biosens. Bioelectron.
(2008)
A. Díaz-Fernández et al.
Biosens. Bioelectron.
(2019)
K. Yang et al.
Biosens. Bioelectron.
(2017)

T. Cha et al.

Biosens. Bioelectron.

(2014)

P. Jolly et al.

Sens. Actuators, B

(2017)

P. Miao et al.

Sens. Actuators, B

(2018)

C.-Y. Lee et al.

Sens. Actuators, B

(2018)

A. Raouafi et al.

Sens. Actuators, B

(2019)

W. Argoubi et al.

Sens. Actuators, B

(2018)

A. Rahi et al.

Talanta

(2016)

J.-T. Cao et al.

Biosens. Bioelectron.

(2018)

M. Souada et al.

Biosens. Bioelectron.

(2015)

P. Jolly et al.

Biosens. Bioelectron.

(2016)

E. Heydari-Bafrooei et al.

Biosens. Bioelectron.

(2017)

B. Kavosi et al.

Biosens. Bioelectron.

(2015)

P. Jolly et al.

Biosens. Bioelectron.

(2016)

Z. Chen et al.

Biosens. Bioelectron.

(2012)

B. Wei et al.

Biosens. Bioelectron.

(2018)

P. Jolly et al.

Sens. Actuators, B

(2015)

G.M. Gersuk et al.

Biochem. Biophys. Res. Commun.

(1997)

M. Negahdary et al.

Biochem. Eng. J.

(2019)

J.H. Choi et al.

Biosens. Bioelectron.

(2013)

I. Strzemińska et al.

Biosens. Bioelectron.

(2016)

Z. Tang et al.

Biosens. Bioelectron.

(2017)

H. Qi et al.

Talanta

(2012)

P. Karami et al.

Talanta

(2019)

S. Barman et al.

Biosens. Bioelectron.

(2018)

Q. Fang et al.

Electrochim. Acta

(2019)

M.S. Khan et al.

Anal. Biochem.

(2019)

B. Li et al.

Anal. Chim. Acta

(2018)

A. Liu et al.

Biosens. Bioelectron.

(2016)

M. García-Cortés et al.

Anal. Chim. Acta

(2017)

Y.-X. Dong et al.

Biosens. Bioelectron.

(2017)

P. Karami et al.

Spectrochim. Acta Part A Mol. Biomol. Spectrosc.

(2019)

Y. Wei et al.

Biosens. Bioelectron.

(2019)

X.-L. Huo et al.

Electrochem. Commun.

(2019)

L. Deng et al.

Electrochem. Commun.

(2015)

J. Li et al.

Biosens. Bioelectron.

(2015)

Y. Liu et al.

Anal. Chim. Acta

(2017)

H. Ma et al.

Biosens. Bioelectron.

(2016)

H. Ma et al.

Biosens. Bioelectron.

(2016)

H. Ma et al.

Talanta

(2018)

M.N. Bashir

Asian Pac. J. Cancer Prev.

(2015)

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New technologies have provided suitable tools for rapid diagnosis of cancer which can reduce treatment costs and even increase patients’ survival rates. Recently, the development of electrochemical aptamer-based nanobiosensors has raised great hopes for early, sensitive, selective, and low-cost cancer diagnosis. Here, we reviewed the flagged recent research (2021–2023) developed as a series of biosensors equipped with nanomaterials and aptamer sequences (nanoaptasensors) to diagnose/prognosis of various types of cancers. Equipping these aptasensors with nanomaterials and using advanced biomolecular technologies have provided specified biosensing interfaces for more optimal and reliable detection of cancer biomarkers. The primary intention of this review was to present and categorize the latest innovations used in the design of these diagnostic tools, including the hottest surface modifications and assembly of sensing bioplatforms considering diagnostic mechanisms. The main classification is based on applying various nanomaterials and sub-classifications considered based on the type of analyte and other vital features. This review may help design subsequent electrochemical aptasensors. Likewise, the up-to-date status, remaining limitations, and possible paths for translating aptasensors to clinical cancer assay tools can be clarified.
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However, the use of antibodies comes with drawbacks, including high cost, intractable conditions and high time consumption, which limits their development for practical applications. Especially, tumor-derived exosomes are pooled together with exosomes from healthy cells in the circulatory system(Cheng et al., 2022), which means low levels of PCa-related biomarkers from healthy exosomes, like miRNAs and proteins, may disturb the detection signals from tumor-derived exosomes, thereby biasing the actual detection results(Li et al., 2019a; Negahdary et al., 2020). Therefore, there is a great need to specifically enrich tumor-derived exosomes from a large pool of healthy cell-derived exosomes.
Prostate specific membrane antigen (PSMA)-positive exosomes have the potential to serve as highly sensitive biomarkers for prostate cancer detection. Herein, a sensitive electrochemical biosensor for the ultrasensitive detection of PSMA-positive exosomes has been constructed based on a peptide-templated AgNPs nanoprobe. In this work, PSMA-specific binding peptides immobilized on a gold electrode were responsible for prostate cancer-derived exosomes capturing. Well-designed peptide (CCY- LWYIKC) serves a dual role: as a signal probe and as a recognizer in the exosomes-identification process. Specifically, LWYIKC bind to cholesterol at the exosome membranes, and CCY function as peptide templates to host a large number of silver nanoparticles, leading to a strong electrochemical signal. Thus, the concentration of exosomes can be quantified via electrochemical signal. This innovative method displayed a wide detection range of 10² to 10⁸ particles/μL and a detection limit as low as 37 particles/μL. Notably, the method has shown outstanding performance when validated using clinical samples, suggesting its potential for clinical applications.
Recent electrochemical sensors and biosensors for toxic agents based on screen-printed electrodes equipped with nanomaterials
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Fast and accurate detection of toxic substances can effectively increase the quality of human life, life expectancy, and environmental protection. So far, many electrochemical (bio)sensors have been designed to provide optimal (simplicity, low cost, high selectivity, and high sensitivity) detection of toxic substances. Here, the latest (2021 and 2022) electrochemical (bio) sensors involving nanomaterials-based SPEs for detecting toxic species are categorized and reviewed. The main application of nanomaterials was found as an increasing diagnostic sensitivity agent. Toxic substances were investigated and categorized into several groups: toxins, toxic inorganic species, pesticides and other organic residues, and drugs. Evidently, toxicity depends on the dose of each substance, and unwanted doses, even for drugs. The specific features of diagnostic platforms, the application of various nanomaterials, and diagnostic strategies were included. Moreover, the crucial specifications of all electrochemical (bio)sensors that have recently been developed to detect toxic substances have been presented in several tables considering the type of analyte.
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Recent studies have highlighted essential advantages of using short peptides as promising alternatives to antibodies for biological recognition elements in biosensors, such as easy modification, chemical versatility, high stability and low-cost [14–17]. Such peptide-based biosensors, which are first termed as peptisensors by Heli et al. in 2019 [18], have been developed rapidly for sensing various biomarkers during the past several years [19–23]. For PSA assays, studies have shown that PSA can recognize a peptide sequence of QLKSSH with enzymatic activity that can catalyze site-specific cleavage reaction [24].
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ReviewAdvances in prostate specific antigen biosensors-impact of nanotechnology

Highlights

Abstract

Introduction

Section snippets

PSA aptasensors

PSA peptisensors

PSA immunosensors

Other PSA biosensors

Conclusion

Perspectives

Acknowledgments

Lancet

Biosens. Bioelectron.

Sens. Actuators, B

Adv. Drug Deliv. Rev.

Anal. Biochem.

Biosens. Bioelectron.

Gold Bull.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Sens. Actuators, B

Sens. Actuators, B

Sens. Actuators, B

Sens. Actuators, B

Sens. Actuators, B

Talanta

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Sens. Actuators, B

Biochem. Biophys. Res. Commun.

Biochem. Eng. J.

Biosens. Bioelectron.

Biosens. Bioelectron.

Biosens. Bioelectron.

Talanta

Talanta

Biosens. Bioelectron.

Electrochim. Acta

Anal. Biochem.

Anal. Chim. Acta

Biosens. Bioelectron.

Anal. Chim. Acta

Biosens. Bioelectron.

Spectrochim. Acta Part A Mol. Biomol. Spectrosc.

Biosens. Bioelectron.

Electrochem. Commun.

Electrochem. Commun.

Biosens. Bioelectron.

Anal. Chim. Acta

Biosens. Bioelectron.

Biosens. Bioelectron.

Talanta

Asian Pac. J. Cancer Prev.

Review
Advances in prostate specific antigen biosensors-impact of nanotechnology