Navegando por Palavras-chave "Peptídeos Terapêuticos"

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    Funcionalização De Nanopartículas Metálicas Com Diferentes Combinações De Peptídeos Para Aplicações Como Agentes Antimicrobianos E Antitumorais
    (Universidade Federal de São Paulo (UNIFESP), 2017-11-27) Formaggio, Daniela Maria Ducatti [UNIFESP]; Tada, Dayane Batista [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Metal nanoparticles (NPs) have showing promising applications in the biomedical field. These NPs have unique physicochemical properties, as well as great chemical versatility on their surface, which allows new modifications and incorporations of different molecules. In addition, they have the advantage of accumulating preferentially in tumor tissues due to the enhanced permeability and retention effect, known as EPR. The incorporation of therapeutic peptides to the surface of metallic NPs could be a promising strategy to improve their applications as therapeutic molecules. Peptides are highly selective molecules. However, they are also vulnerable to some in vivo pharmacologic barriers limiting their effective action, including low bioavailability or deactivation by enzymes. In this work, three types of metal NPs were prepared: gold NPs (AuNPs), silver NPs (AgNPs) and bimetallic NPs composed by gold and platinum (AuPtNPs). NPs were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP-OES) and X-ray diffraction (XRD). Aiming at biomedical applications, NPs were firstly evaluated regarding their toxicity by cell viability assays using human fibroblast cells (HS68 cell line) and embryonic toxicity test in zebrafish (Danio rerio). The assays showed better biocompatibility of AuNPs compared to AgNPs and AuPtNPs. Thus, AuNPs were studied as carriers of antitumor and antimicrobial peptides as an alternative approach of overcoming the pharmacokinetic limitations inherent in these molecules. Two peptides derived from complementary monoclonal antibodies (CDRs) with amino acid sequences YISCYNGATSYNQKFK (C7H2) and RASQSVSSYLA (HuAL1) were previously identified by collaborators of this project demonstrating excellent toxicity against tumor cells, antimetastatic activity as well as a potent antimicrobial activity. The peptides were individually conjugated to the AuNPs surface, forming the AuNPsC7H2 and AuNPsHuAL1 NPs. The peptides were also linked together forming the AuNPsC7H2HuAL1. The in vitro results suggested an improved antitumor activity for AuNPsHuAL1 and AuNPsC7H2HuAL1 against metastatic melanoma tumor cell line (B16F10-Nex2) compared to the peptides in solution. In vivo, the peptide combination of HuAL1 and C7H2 was even more efficient when linked to AuNPs. The antimicrobial activity of the three NPs separately as well as the peptide functionalized AuNPs were also evaluated employing microdilution test against strains of Candida Albicans, Pseudomonas aeruginosa and Staphylococcus aureus. The results confirm an intrinsic antimicrobial action of the three metal NPs and an optimal antibiotic action for AuNPsHuAL1.