A new 8-oxo-7,8-2′deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine

Luis Pla; Félix Sancenón; M. Carmen Martínez-Bisbal; Celia Bañuls; Nuria Estañ; Marina Botello-Marabotto; Elena Aznar; Guillermo Sáez; Sara Santiago-Felipe; Ramón Martínez-Máñez

doi:10.1039/D0NR07948K

A new 8-oxo-7,8-2′deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine†

Luis Pla,

^abc Félix Sancenón,

^abcde M. Carmen Martínez-Bisbal,

*^abcdf Celia Bañuls,

^g Nuria Estañ,^hi Marina Botello-Marabotto,

^bc Elena Aznar,

^abcde Guillermo Sáez,

^hi Sara Santiago-Felipe

*^abc and Ramón Martínez-Máñez

*^abcde

Author affiliations

* Corresponding authors

^a CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain

^b Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico, Universitat Politècnica de València – Universitat de València, Camino de Vera s/n, Valencia, Spain
E-mail: carmen.martinez-bisbal@uv.es, sasanfe@upvnet.upv.es, rmaez@qim.upv.es

^c Unidad Mixta de Investigación en Nanomedicina y Sensores. Universitat Politècnica de València – Instituto de Investigación Sanitaria La Fe, Valencia, Spain

^d Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina. Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, Valencia, Spain

^e Departamento de Química, Universitat Politècnica de València, Valencia, Spain

^f Departamento de Química Física. Universitat de València, Burjasot, Valencia, Spain

^g Servicio de Endocrinología y Nutrición. Hospital Universitario Dr Peset-FISABIO, Valencia, Spain

^h Departamento de Bioquímica y Biología Molecular, Facultad de Medicina y Odontología-INCLIVA, Universitat de València, Valencia, Spain

ⁱ Servicio de Análisis Clínicos, Hospital Universitario Dr Peset-FISABIO, Valencia, Spain

Abstract

Many important human diseases, and especially cancer, have been related to the overproduction of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG). This molecule is a product of oxidative stress processes over nucleophilic bases in DNA. In this work, an aptasensor for the rapid, selective and accurate detection of this oncomarker is presented. The aptasensor consists of a nanoporous anodic alumina material loaded with a dye and is functionalized with an aptamer-based “molecular gate”. In the presence of target 8-oxo-dG, the capping aptamer displaces from the surface due to the high affinity of the analyte with the capping aptamer, thus inducing delivery of the preloaded fluorescent dye. In contrast, in the absence of 8-oxo-dG, a poor payload delivery is accomplished. This aptamer-based nanodevice has great sensitivity for 8-oxo-dG, resulting in a LOD of 1 nM and a detection time of ca. 60 min. Moreover, the aptasensor is able to accurately detect 8-oxo-dG in unmodified urine and serum without pre-concentration treatments. This diagnostic tool is validated in a set of 38 urine and serum samples from patients diagnosed of colorectal cancer and control patients. These samples are also analyzed using a standardized and specific ELISA kit. The aptasensor displays excellent sensitivity (95.83/100%) and specificity (80/100%) for 8-oxo-dG detection in serum and urine samples, respectively. Our results may serve as a basis for the development of generalized fluorogenic diagnostic platforms for the easy diagnosis of cancer in biofluids as well as for monitoring therapeutic treatments and detection of relapses without the use of expensive equipment or trained personnel.

Nanoscale

A new 8-oxo-7,8-2′deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine†

Abstract

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A new 8-oxo-7,8-2′deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine

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