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Synthesis and functionalization of bimetallic nanoparticles for application in photodynamic therapy of cancer

Grant number: 17/01697-6
Support type:Regular Research Grants
Duration: September 01, 2017 - August 31, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Dayane Batista Tada
Grantee:Dayane Batista Tada
Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
Assoc. researchers:Denise Costa Arruda ; Katia da Conceição ; Mauricio da Silva Baptista
Associated scholarship(s):18/02511-6 - Technical training in cell culture and in vitro assays, BP.TT

Abstract

Despite the continuous development of Photodynamic Therapy of cancer, the consolidation of this therapy in clinical application is hold back due to the unsatisfactory tumor targeting and short circulation time of photosensitizers (FS). The coupling of FS to nanoparticles (NPs) has emerged as a useful tool to overcome these limitations. The NPs have enhanced penetration and retention in tumors due to their irregular vasculature and their larger porous compared to the normal tissues. Additionally, to the improved tumor targeting, NPs can enhance therapeutic efficiency of FS by protecting them from deactivation, avoiding FS aggregation and providing the control of FS photoactivity. As an example, metallic surfaces can enhance the efficiency of FS in generating reactive oxygen species, especially singlet oxygen, which is known to cause cellular death through apoptosis. Although this effect has been reported for monometallic NPs, the use of bimetallic NPs to control FS photoactivity was poorly explored until now. Since the optical and catalytic properties of bimetallic NPs has been shown to be superior than the properties of monometallic NPs, it is expected that bimetallic NPs will be more efficient in enhancing FS photoactivity. In this way, it is proposed in this project the synthesis of bimetallic NPs and their functionalization with a FS with the goal of obtaining photosensitizing NPs of high photoactivity. Besides that, it is expected that these NPs will present better tumor targeting not only by passive mechanism but also by active mechanism since the peptide C (CVNHPAFAC), which was previously identified as a tumor-homing peptide, will also be linked to the NPs surface. Another advantage of bimetallic NPs is their superior antimicrobial activity. For this reason, it is also expected that the NPs to be developed in this project will present antimicrobial activity, which can avoid infectious processes during treatment. Photosensitizing NPs will be developed based on the following bimetallic combinations: gold and silver, silver and iron and gold and platinum. Aiming at the improved antitumoral activity of these NPs, their surface will be additionally functionalized with the peptides YISCYNGATSYNQKFK, RASQSVSSYLA e GQYGNLWFAY. These peptides had their antitumoral and antimetastatic activities in vivo demonstrated in previous works. Following the morphological, photophysical and photochemical characterization, the photoactivity of the NPs developed here will be evaluated through in vitro assays with murine metastatic melanoma cells. (AU)

Scientific publications
(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)
DA SILVA, DIEGO MORAIS; CANUTO DE MENEZES, BEATRIZ ROSSI; NONATO BEZZON, VINICIUS DANILO; DO AMARAL MONTANHEIRO, THAIS LARISSA; DE MACEDO, ERENILDA FERREIRA; TADA, DAYANE BATISTA; PETRACONI, GILBERTO; THIM, GILMAR PATROCINIO. Phase transition of TiO2 nanoparticles into titanate nanorods via hydrothermal reactions. SN APPLIED SCIENCES, v. 1, n. 8 AUG 2019. Web of Science Citations: 0.
DE MACEDO, ERENILDO FERREIRA; DUCATTI FORMAGGIO, DANIELA MARIA; SANTOS, NIVIA SALLES; TADA, DAYANE BATISTA. Gold Nanoparticles Used as Protein Scavengers Enhance Surface Plasmon Resonance Signal. SENSORS, v. 17, n. 12 DEC 2017. Web of Science Citations: 4.

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