Doxorubicin Anticancer Drug Monitoring by ds-DNA-Based Electrochemical Biosensor in Clinical Samples

Moghadam, Firouzeh Hassani; Taher, Mohammad Ali; Karimi-Maleh, Hassan

doi:10.3390/mi12070808

Cited by 32 publications

(17 citation statements)

References 55 publications

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“…In this sense, Kulikova et al [40] mention that the changes in the current caused by Dox depend on the amount of DNA detected. On the other hand, our results show that the incubation time with Dox is sufficient to indicate the detection process of the double-stranded DNA, as reported by Hassani Moghadam et al [41] where they confirmed that in 20 minutes Dox intercalates the doublestranded DNA. Moreover, Ma et al [42] obtained similar results to ours.…”

Section: Electrochemical Detectionsupporting

confidence: 87%

Detection of the p53 Gene Mutation Using an Ultra-sensitive and Highly Selective Electrochemical DNA Biosensor

et al. 2023

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Abstract. The p53 gene— “the guardian of the genome”—is responsible for maintaining the integrity of the genome, along with cell cycle regulation, apoptosis, and cell differentiation. New analytical devices are needed to recognize the main alterations this gene could suffer, since it is one of the most frequent in human cancer. For this reason, we developed an electrochemical DNA biosensor with high sensitivity and specificity to monitor the 175p2 mutation of the p53 gene. We modified a screen-printed gold electrode (SPGE) by immobilizing a thiolated DNA probe sequence with 11-mercaptoundecanoic acid to detect its complementary sequence through the hybridization reaction. Doxorubicin (Dox) was used to increase the sensitivity of the biosensor, and the entire process was evaluated using the Cyclic Voltammetry (CV) technique. The measurement range of the developed device is from 1 fM to 100 nM of the p53 gene mutation with a limit of detection (LOD) of 2.2 fM. In the presence of Dox, the LOD increased up to 175 aM, becoming one of the highest efficiency devices in the field. The electrochemical DNA biosensor selectively detects the p53 suppressor gene mutation; it distinguishes between different non-complementary and complementary sequences. Our results indicate a high potential of our sensor for the p53 gene 175p2 mutation detection, which is convenient in the early diagnosis of diseases related to this gene. Resumen. El gen p53—“guardián del genoma”—es responsable de mantener la integridad del genoma, así como de la regulación del ciclo celular, la apoptosis, y la diferenciación celular. Es necesario desarrollar nuevos dispositivos analíticos para reconocer las principales alteraciones que este gen podría sufrir, ya que es uno de los más frecuentes en el cáncer humano. En este sentido, se desarrolló un sensor electroquímico de ADN de alta sensibilidad y especificidad para identificar la mutación 175p2 del gen p53. Para ello, se formó una monocapa sobre un electrodo de oro que contenía secuencias sonda de ADN tiolado junto con ácido 11-mercaptoundecanoico, las cuales se emplearon para detectar la mutación del gen a través de la reacción de hibridación. Finalmente, se utilizó doxorrubicina (Dox) para aumentar la sensibilidad del biosensor; el proceso se evaluó mediante la técnica de Voltamperometría Cíclica (VC). El rango de medición del dispositivo desarrollado es de 1 fM a 100 nM de la mutación del gen p53 con un límite de detección (LOD) de 2.2 fM. En presencia de Dox, el LOD aumentó hasta 175 aM, convirtiéndose en uno de los dispositivos de mayor eficiencia en el campo. El biosensor electroquímico de ADN detecta selectivamente la mutación del gen supresor p53 y es capaz de distinguir entre diferentes secuencias complementarias y no complementarias. Nuestros resultados indican un alto potencial del biosensor para la detección de la mutación 175p2 del gen p53, lo cual es conveniente en el diagnóstico oportuno de enfermedades relacionadas con este gen.

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Section: Electrochemical Detectionsupporting

confidence: 87%

Detection of the p53 Gene Mutation Using an Ultra-sensitive and Highly Selective Electrochemical DNA Biosensor

et al. 2023

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“…Nevertheless, high sensitivity of the response to doxorubicin can be mentioned. The LOD found was lower than the characteristics of DNA sensors based on redox active polymers of carbonaceous nanomaterials, where the doxorubicin reaction resulted in changes in intrinsic redox activity of the layer (poly(Azure B), 90 pM [39]; poly(neutral red), 100 pM [40]; carbon nanotubes-polylysine, 100 nM [41]; and single-walled carbon nanotubes 60, pM [42]). It should be noted that the reaction with doxorubicin was used in this study to confirm the introduction of DNA in the surface layer and its interaction with the TC molecules.…”

Section: Hydroquinonementioning

confidence: 76%

Electrochemical Sensing of Interactions between DNA and Charged Macrocycles

et al. 2021

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In this work, we investigated aggregation of native DNA and thiacalix[4]arene derivative bearing eight terminal amino groups in cone configuration using various redox probes on the glassy carbon electrode. It was shown that sorption transfer of the aggregates on the surface of the electrode covered with carbon black resulted in changes in electrostatic interactions and diffusional permeability of the surface layer. Such changes alter the signals of ferricyanide ion, methylene green and hydroquinone as redox probes to a degree depending on their specific interactions with DNA and own charge. Inclusion of DNA in the surface layer was independently confirmed by scanning electron microscopy, electrochemical impedance spectroscopy and experiments with doxorubicin as a model intercalator. Thermal denaturing of DNA affected the charge separation on the electrode interface and the signals of redox probes. Using hydroquinone, less sensitive to electrostatic interactions, made it possible to determine from 10 pM to 1.0 nM doxorubicin (limit of detection 3 pM) after 10 min incubation. Stabilizers present in the commercial medications did not alter the signal. The DNA sensors developed can find future application in the assessment of the complexes formed by DNA and macrocycles as delivery agents for small chemical species.

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“…42 Also, DOX is particularly suitable for loading on DNA-based nanocarriers because it intercalates into the minor groove of double-stranded DNA. 43 The low pH in tumor microenvironment (TME) is shared by healthy joints, 44 intracellular milieu, 11 and the stomach. pH-responsive drug release lacks tumor specificity.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…DOX is commonly used to as a model drug to test the drug delivery system owing to its excellent antitumor effect and fluorescence property . Also, DOX is particularly suitable for loading on DNA-based nanocarriers because it intercalates into the minor groove of double-stranded DNA . The low pH in tumor microenvironment (TME) is shared by healthy joints, intracellular milieu, and the stomach.…”

Section: Resultsmentioning

confidence: 99%

Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions

Deng

Tan

Zhang

et al. 2022

ACS Appl. Mater. Interfaces

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DNA nanostructure-based responsive drug delivery has become an increasingly potent method in cancer therapy. However, a variety of important cancer biomarkers have not been explored in searching of new and efficient targeted delivery systems. Uracil degradation glycosylase and human apurinic/apyrimidinic endonuclease are significantly more active in cancer cells. Here, we developed uracil-modified DNA nanotubes that can deliver drugs to tumor cells through an enzyme-induced disassembly process. Although the reaction of these enzymes on their natural DNA substrates has been established, their reactivity on self-assembled nanostructures of nucleic acids is not well understood. We leveraged molecular dynamic simulation based on coarse-grained model to forecast the enzyme reactivity on different DNA designs. The experimental data are highly consistent with the simulation results. It is the first example of molecule simulation being used to guide the design of enzyme-responsive DNA nano-delivery systems. Importantly, we found that the efficiency of drug release from the nanotubes can be regulated by tuning the positions of uracil modification. The DNA nanotubes equipped with cancerspecific aptamer AS1411 are used to deliver doxorubicin to tumor-bearing mice not only effectively inhibiting tumor growth but also protecting major organs from drug-caused damage. We believe that this work provides new knowledge on and insights into future design of enzyme-responsive DNA-based nanocarriers for drug delivery.

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Doxorubicin Anticancer Drug Monitoring by ds-DNA-Based Electrochemical Biosensor in Clinical Samples

Cited by 32 publications

References 55 publications

Detection of the p53 Gene Mutation Using an Ultra-sensitive and Highly Selective Electrochemical DNA Biosensor

Detection of the p53 Gene Mutation Using an Ultra-sensitive and Highly Selective Electrochemical DNA Biosensor

Electrochemical Sensing of Interactions between DNA and Charged Macrocycles

Design of Uracil-Modified DNA Nanotubes for Targeted Drug Release via DNA-Modifying Enzyme Reactions

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