Synthesis and functionalization of metallic and bimetallic nanoparticles to modula...
| 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)