CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients?
D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H<sub>2</sub>O<sub>2</sub>. The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1477 |
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| author | María Fuentes-Baile Elizabeth Pérez-Valenciano Pilar García-Morales Camino de Juan Romero Daniel Bello-Gil Víctor M. Barberá Álvaro Rodríguez-Lescure Jesús M. Sanz Cristina Alenda Miguel Saceda |
| author_facet | María Fuentes-Baile Elizabeth Pérez-Valenciano Pilar García-Morales Camino de Juan Romero Daniel Bello-Gil Víctor M. Barberá Álvaro Rodríguez-Lescure Jesús M. Sanz Cristina Alenda Miguel Saceda |
| author_sort | María Fuentes-Baile |
| collection | DOAJ |
| description | D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H<sub>2</sub>O<sub>2</sub>. The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several pancreatic and colorectal carcinoma and glioblastoma cell models. In the current work, we determined whether the effect of CLytA-DAAO immobilized in magnetic nanoparticles, gold nanoparticles, and alginate capsules offered some advantages as compared to the free CLytA-DAAO. Results indicate that the immobilization of CLytA-DAAO in magnetic nanoparticles increases the stability of the enzyme, extending its time of action. Besides, we compared the effect induced by CLytA-DAAO with the direct addition of hydrogen peroxide, demonstrating that the progressive generation of reactive oxygen species by CLytA-DAAO is more effective in inducing cytotoxicity than the direct addition of H<sub>2</sub>O<sub>2</sub>. Furthermore, a pilot study has been initiated in biopsies obtained from pancreatic and colorectal carcinoma and glioblastoma patients to evaluate the expression of the main genes involved in resistance to CLytA-DAAO cytotoxicity. Based on our findings, we propose that CLytA-DAAO immobilized in magnetic nanoparticles could be effective in a high percentage of patients and, therefore, be used as an anti-cancer therapy for pancreatic and colorectal carcinoma and glioblastoma. |
| first_indexed | 2024-03-09T06:05:35Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:05:35Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f13ae5ae9884743bd5561643e943bae2023-12-03T12:04:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01223147710.3390/ijms22031477CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients?María Fuentes-Baile0Elizabeth Pérez-Valenciano1Pilar García-Morales2Camino de Juan Romero3Daniel Bello-Gil4Víctor M. Barberá5Álvaro Rodríguez-Lescure6Jesús M. Sanz7Cristina Alenda8Miguel Saceda9Unidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, Elche, 03203 Alicante, SpainDepartamento de Bioquímica y Biología Molecular, Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, SpainDepartamento de Bioquímica y Biología Molecular, Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, SpainUnidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, Elche, 03203 Alicante, SpainDepartamento de Bioquímica y Biología Molecular, Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Avda, Universidad s/n, Ed. Torregaitán, Elche, 03202 Alicante, SpainUnidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, Elche, 03203 Alicante, SpainServicio de Oncología, Hospital General Universitario de Elche, Elche, 03203 Alicante, SpainCentro de Investigaciones Biológicas Margarita Salas (Consejo Superior de Investigaciones Científicas) and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), C/Ramiro de Maeztu, 9, 28040 Madrid, SpainUnidad de Investigación, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Hospital General Universitario de Alicante, C/Maestro Alonso, 10, 03010 Alicante, SpainUnidad de Investigación, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO), Hospital General Universitario de Elche, Camí de l’Almazara 11, Elche, 03203 Alicante, SpainD-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H<sub>2</sub>O<sub>2</sub>. The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several pancreatic and colorectal carcinoma and glioblastoma cell models. In the current work, we determined whether the effect of CLytA-DAAO immobilized in magnetic nanoparticles, gold nanoparticles, and alginate capsules offered some advantages as compared to the free CLytA-DAAO. Results indicate that the immobilization of CLytA-DAAO in magnetic nanoparticles increases the stability of the enzyme, extending its time of action. Besides, we compared the effect induced by CLytA-DAAO with the direct addition of hydrogen peroxide, demonstrating that the progressive generation of reactive oxygen species by CLytA-DAAO is more effective in inducing cytotoxicity than the direct addition of H<sub>2</sub>O<sub>2</sub>. Furthermore, a pilot study has been initiated in biopsies obtained from pancreatic and colorectal carcinoma and glioblastoma patients to evaluate the expression of the main genes involved in resistance to CLytA-DAAO cytotoxicity. Based on our findings, we propose that CLytA-DAAO immobilized in magnetic nanoparticles could be effective in a high percentage of patients and, therefore, be used as an anti-cancer therapy for pancreatic and colorectal carcinoma and glioblastoma.https://www.mdpi.com/1422-0067/22/3/1477enzymatic therapyreactive oxygen speciesmagnetic nanoparticlegold nanoparticlealginate capsuleshydrogen peroxide |
| spellingShingle | María Fuentes-Baile Elizabeth Pérez-Valenciano Pilar García-Morales Camino de Juan Romero Daniel Bello-Gil Víctor M. Barberá Álvaro Rodríguez-Lescure Jesús M. Sanz Cristina Alenda Miguel Saceda CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? International Journal of Molecular Sciences enzymatic therapy reactive oxygen species magnetic nanoparticle gold nanoparticle alginate capsules hydrogen peroxide |
| title | CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? |
| title_full | CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? |
| title_fullStr | CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? |
| title_full_unstemmed | CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? |
| title_short | CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients? |
| title_sort | clyta daao chimeric enzyme bound to magnetic nanoparticles a new therapeutical approach for cancer patients |
| topic | enzymatic therapy reactive oxygen species magnetic nanoparticle gold nanoparticle alginate capsules hydrogen peroxide |
| url | https://www.mdpi.com/1422-0067/22/3/1477 |
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