RESUMO
Although photodynamic therapy (PDT) of cancer has been continuously improved, its efficiency is still limited by the high toxicity in the absence of irradiation, aggregation and deactivation by biomolecules of the most common photosensitizers (PS). The association of PS to nanoparticles (NPs) can be a promising tool to overcome these limitations and also to enhance PS tumoral selectivity. In addition, the association of PS to metallic NPs may provide the modulation of PS fluorescence and also the enhancement of PS photoactivity due to the electronic coupling with NPs plasmon effect. Adversely to the innumerous work on the coupling of PS to metallic NPs, the application of bimetallic NPs with this goal has not been explored yet. In this work we investigated the physicochemical properties and cytotoxicity of bimetallic gold-platinum NPs (AuPtNPs) conjugated to a chlorin molecule modified with a thiol group. Additionally, chlorin was coupled to AuNPs for comparative purposes since these have been the most commonly used NPs in PDT. The results showed that both platforms promoted the chlorin solubility in water which is crucial in biological applications. Despite the enhancement of photoactivity promoted by both NPs in comparison with chlorin in solution, chlorin-conjugated with AuPtNPs proved to be a more suitable platform for PDT application, since it showed a lower dark citotoxicity, as well as a higher generation of singlet oxygen and cell internalization compared with chlorin-conjugated AuNPs. It is important to highlight that this is the first work reporting on the enhancement of PS photoactivity by its conjugation to AuPtNPs.
RESUMO
Despite the potential antimicrobial activity of metallic nanoparticles, the increasing concerns about nanosafety have been holding back the use of these materials in therapeutics and biomedical devices. In the last years, several studies called attention to metallic nanoparticles toxicity. In the most part of in vitro studies performed with mammalian cells, metallic NPs reduced cell viability and induced genotoxicity and inflammatory responses. Bimetallic NPs have attracted great attention because they present distinct and even more advanced characteristics when compared to nanoparticles formed by a single metal. Recently, bimetallic NPs have emerged as an alternative to improve the antimicrobial activity of metallic nanoparticles, aiming at the broadening of the action spectrum and the reduction of the toxicity. However, the biocompatibility of bimetallic nanoparticles has been demonstrated only by in vitro studies. In the present work, the toxicity of AuPt nanoparticles was addressed both in vitro and in vivo. In addition, the antimicrobial activity of AuPt bimetallic nanoparticles has been evaluated in comparison with Au and Ag nanoparticles. The nanoparticles were characterized by ultraviolet-visible spectroscopy, dynamic light scattering, transmission electron microscopy, inductively coupled plasma optical emission spectroscopy, and X-ray diffraction. The antimicrobial activity was studied against Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. The toxicity of nanoparticles was evaluated in vitro by analyzing their toxicity against human fibroblast cells (HS68 cell line) and in vivo by embryonic toxicity test in zebrafish (Danio rerio). The results confirmed the intrinsic antimicrobial activity of the three types of nanoparticles but different toxicity. Bimetallic nanoparticles showed enhanced antimicrobial activity in comparison with Au nanoparticles but lower antimicrobial activity compared with Ag nanoparticles. However, AuPt nanoparticles showed great advantage over Ag nanoparticles due to the absence of cytotoxicity and lower toxicity in vivo.
RESUMO
Despite the potential antimicrobial activity of metallic nanoparticles, the increasing concerns about nanosafety have been holding back the use of these materials in therapeutics and biomedical devices. In the last years, several studies called attention to metallic nanoparticles toxicity. In the most part of in vitro studies performed with mammalian cells, metallic NPs reduced cell viability and induced genotoxicity and inflammatory responses. Bimetallic NPs have attracted great attention because they present distinct and even more advanced characteristics when compared to nanoparticles formed by a single metal. Recently, bimetallic NPs have emerged as an alternative to improve the antimicrobial activity of metallic nanoparticles, aiming at the broadening of the action spectrum and the reduction of the toxicity. However, the biocompatibility of bimetallic nanoparticles has been demonstrated only by in vitro studies. In the present work, the toxicity of AuPt nanoparticles was addressed both in vitro and in vivo. In addition, the antimicrobial activity of AuPt bimetallic nanoparticles has been evaluated in comparison with Au and Ag nanoparticles. The nanoparticles were characterized by ultraviolet-visible spectroscopy, dynamic light scattering, transmission electron microscopy, inductively coupled plasma optical emission spectroscopy, and X-ray diffraction. The antimicrobial activity was studied against Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. The toxicity of nanoparticles was evaluated in vitro by analyzing their toxicity against human fibroblast cells (HS68 cell line) and in vivo by embryonic toxicity test in zebrafish (Danio rerio). The results confirmed the intrinsic antimicrobial activity of the three types of nanoparticles but different toxicity. Bimetallic nanoparticles showed enhanced antimicrobial activity in comparison with Au nanoparticles but lower antimicrobial activity compared with Ag nanoparticles. However, AuPt nanoparticles showed great advantage over Ag nanoparticles due to the absence of cytotoxicity and lower toxicity in vivo.
