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Use of gold nanoparticles as theranostic agent for atherosclerosis

Abstract

Atherosclerosis is a chronic degenerative disease that affects medium and large caliber arteries, and is characterized by lesions with plaque or atheroma. It is the primary cause of heart diseases and strokes, which are the global leading causes of death by disease.A recent study of our group found that atheromatous plaques exhibit an accumulation of protoporphyrin IX, or PPIX, which is transferred to the blood and feces. This study identified a potential marker for atherosclerosis that may facilitate minimally invasive and cost effective diagnostic method.This project aims to elucidate the mechanisms of PPIX accumulation in atheromatous plaques, which will help in early diagnosis of cardiac diseases. Furthermore, we intend to associate a precursor of the PPIX, the aminolevulinic acid, to gold nanoparticles (ALA:Au), to act as a photosensitizing agent for Phothodynamic Therapy, allowing the destruction of plaques. Thus, ALA:Au will act as a theranostic agent.ALA:Au will be synthesized mixing ALA with Tetrachloroauric(III) acid in miliQ water solution followed by photoreduction with light from a Xenon lamp. The best synthesis conditions, such as optimal illumination time, more appropriate pH, most effective temperature and better stoichiometry will be obtained from measurements of UV/Vis optical absorption and electron microscopy. Male New Zealand rabbits will be used to monitor the atherosclerosis staging for 60 days. The animals will be divided into 5 groups: control group (CG) where animals receive normal diet, and control group with ALA (CGALA ); Experimental group (EG), in which the animals will receive a high calorie diet with 1% cholesterol; Experimental group with ALA ( EGALA ) and Experimental Group with ALA:Au ( EGALAAu ). Changes in the animal's arteries throughout the study will be analyzed by optical microscopy techniques. Blood samples and animal feces, and extracted PPIX in different disease stages (early , 20 , 40 and 60 days) will be analyzed. Measurements of the emission intensity of PPIX extracted from both the feces and blood of animals in the region between 575 and 725 nm will be done. Toxicity studies of the ALA:Au compound will also be performed. (AU)

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Scientific publications (10)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COURROL, DANIELLA DOS SANTOS; BORGES LOPES, CARLA REGINA; PACHECO PEREIRA, CAMILA BUENO; FRANZOLI, MARCIA REGINA; DE OLIVEIRA SILVA, FLAVIA RODRIGUES; COURROL, LILIA CORONATO. Tryptophan Silver Nanoparticles Synthesized by Photoreduction Method: Characterization and Determination of Bactericidal and Anti-Biofilm Activities on Resistant and Susceptible Bacteria. INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH, v. 12, . (14/06960-9)
SICCHIERI, LETICIA B.; DA SILVA, MONICA N.; SAMAD, RICARDO E.; COURROL, LILIA C.. Can measurement of the fluorescence lifetime of extracted blood PPIX predict atherosclerosis?. Journal of Luminescence, v. 195, p. 176-180, . (14/06960-9)
SICCHIERI, LETICIA BONFANTE; MONTEIRO, ANDREA MOREIRA; FIGUEIREDO NETO, ANTONIO MARTINS; GOMES, LAERCIO; COURROL, LILIA CORONATO. Optical Properties of Europium Tetracycline Complexes in the Presence of High-Density Lipoproteins (HDL) Subfractions. Applied Spectroscopy, v. 71, n. 7, p. 1560-1567, . (14/06960-9)
DE MATOS, RICARDO ALMEIDA; COURROL, LILIA CORONATO. Biocompatible silver nanoparticles prepared with amino acids and a green method. Amino Acids, v. 49, n. 2, p. 379-388, . (14/06960-9)
COURROL, DANIELLA DOS SANTOS; BORGES LOPES, CARLA REGINA; CORDEIRO, THIAGO DA SILVA; FRANZOLIN, MARCIA REGINA; VIEIRA JUNIOR, NILSON DIAS; SARNAD, RICARDO ELGUL; COURROL, LILIA CORONATO. Optical properties and antimicrobial effects of silver nanoparticles synthesized by femtosecond laser photoreduction. OPTICS AND LASER TECHNOLOGY, v. 103, p. 233-238, . (14/06960-9)
GONCALVES, KARINA DE OLIVEIRA; VIEIRA, DANIEL PEREZ; LEVY, DEBORA; BYDLOWSKI, SERGIO PAULO; COURROL, LILIA CORONATO. Uptake of silver, gold, and hybrids silver-iron, gold-iron and silver-gold aminolevulinic acid nanoparticles by MCF-7 breast cancer cells. Photodiagnosis and Photodynamic Therapy, v. 32, . (14/50983-3, 17/23686-6, 14/06960-9)
COURROL, LILIA CORONATO; SAMAD, RICARDO ELGUL. Determination of chicken meat contamination by porphyrin fluorescence. Journal of Luminescence, v. 199, p. 67-70, . (14/06960-9)
BORGES, CARLA R.; SAMAD, RICARDO E.; GONCALVES, KARINA DE OLIVEIRA; VIEIRA, DANIEL PEREZ; COURROL, LILIA C.. Interaction between protoporphyrin IX and tryptophan silver nanoparticles. JOURNAL OF NANOPARTICLE RESEARCH, v. 20, n. 6, . (14/06960-9)
SICCHIERI, LETICIA BONFANTE; NATAL, RODRIGO DE ANDRADE; COURROL, LILIA CORONATO. Fluorescent lifetime imaging microscopy using Europium complexes improves atherosclerotic plaques discrimination. INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, v. 32, n. 10, p. 1595-1604, . (14/06960-9)
GONCALVES, KARINA DE OLIVEIRA; DE OLIVEIRA SILVA, FLAVIA RODRIGUES; VIEIRA, DANIEL PEREZ; COURROL, LILIA CORONATO. Synthesis and characterization of aminolevulinic acid with gold and iron nanoparticles by photoreduction method for non-communicable diseases diagnosis and therapy. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS, v. 30, n. 18, SI, p. 16789-16797, . (14/06960-9)

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