CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients?

• Published in: International journal of molecular sciences Vol. 22; no. 3; p. 1477
• Main Authors: Fuentes-Baile, María, Pérez-Valenciano, Elizabeth, García-Morales, Pilar, de Juan Romero, Camino, Bello-Gil, Daniel, Barberá, Víctor M, Rodríguez-Lescure, Álvaro, Sanz, Jesús M, Alenda, Cristina, Saceda, Miguel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02-02-2021; MDPI
• Subjects: Alanine; alginate capsules; Alginates; Alginic acid; Amidase; Amino acid oxidase; Amino acids; Apoptosis; Brain cancer; Cell culture; Cell cycle; Cell Line, Tumor; Choline; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - therapy; Cytotoxicity; D-Amino acids; D-Amino-acid oxidase; D-Amino-Acid Oxidase - metabolism; D-Amino-Acid Oxidase - therapeutic use; enzymatic therapy; Enzymes; Gene expression; Glioblastoma; Glioblastoma - therapy; gold nanoparticle; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Immobilization; Kinases; L-Alanine; magnetic nanoparticle; Magnetite Nanoparticles - chemistry; N-Acetylmuramoyl-L-alanine amidase; Nanoparticles; Neoplasms - drug therapy; Neoplasms - therapy; Oxidation; Oxidative stress; Pancreas; Pancreatic cancer; Pancreatic carcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - therapy; Proteins; Quantum dots; reactive oxygen species; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - toxicity; Recombinant Fusion Proteins - chemistry; Streptococcus infections; magnetic nanoparticle; alginate capsules; gold nanoparticle; enzymatic therapy; hydrogen peroxide; reactive oxygen species; cytotoxicity; oxidative stress
• DOI: 10.3390/ijms22031477
• EISSN: 1422-0067
• ISSN: 1422-0067; 1661-6596

D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating H
O
. 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
O
. 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.