RESUMO
Nanoparticles (NPs) physicochemical properties, such as size, shape, surface chemistry, charge, etc., play a critical role in biological systems interactions, which include NPs' cellular uptake, trafficking, activation, and toxicity. Although nano-bio interactions are multifaceted and complex, their assessment is essential for future therapeutic and diagnostic use since being carriers that deliver specific molecules (i.e., active pharmaceutical ingredients and imaging agents) in intracellular sites. The journey of NPs begins by reaching the plasma membrane and entering the cell mainly through endocytosis. After vesicles pinch off the cell membrane, the intracellular trafficking is mediated by a network of cellular endosomes which direct NPs to the different cellular components. Otherwise, NPs or their contents are released into the cytoplasm. In both cases, NPs can pass undetected or be recognized by the cell leading to a pro or anti-inflammatory response. Indeed, the cell response mostly depends on cell type and NPs physicochemical properties. The principal mechanism by which NPs activate the cell response is RONS production. Other mechanism includes signaling pathways modulation related to metabolic and enzymatic reactions, cell transduction, and immune modulation. Hence, the underlying mechanisms of cellular and subcellular interactions in vitro should be performed to provide insights into NPs' effect. This information helps us to improve their synthesis and design to maximize the clinical benefits while minimizing side effects. Most in vitro tests to evaluate NPs' effect in cells were developed focusing on cell dysfunctions, cytotoxicity, genotoxicity, immunogenicity, and cell death.
RESUMO
The search for new strategies to curb the spread of the SARS-CoV-2 coronavirus, which causes COVID-19, has become a global priority. Various nanomaterials have been proposed as ideal candidates to inactivate the virus; however, because of the high level of biosecurity required for their use, alternative models should be determined. This study aimed to compare the effects of two types of nanomaterials gold (AuNPs) and silver nanoparticles (AgNPs), recognized for their antiviral activity and affinity with the coronavirus spike protein using PhiX174 and enveloped Phi6 bacteriophages as models. To reduce the toxicity of nanoparticles, a species known for its intermediate antiviral activity,Solanum mammosumL. (Sm), was used. NPs prepared with sodium borohydride (NaBH4) functioned as the control. Antiviral activity against PhiX174 and Phi6 was analyzed using its seed, fruit, leaves, and essential oil; the leaves were the most effective on Phi6. Using the aqueous extract of the leaves, AuNPs-Sm of 5.34 ± 2.25 nm and AgNPs-Sm of 15.92 ± 8.03 nm, measured by transmission electron microscopy, were obtained. When comparing NPs with precursors, both gold(III) acetate and silver nitrate were more toxic than their respective NPs (99.99% at 1 mg ml-1). The AuNPs-Sm were less toxic, reaching 99.30% viral inactivation at 1 mg ml-1, unlike the AgNPs-Sm, which reached 99.94% at 0.01 mg ml-1. In addition, cell toxicity was tested in human adenocarcinoma alveolar basal epithelial cells (A549) and human foreskin fibroblasts. Gallic acid was the main component identified in the leaf extract using high performance liquid chromatography with diode array detection (HPLC-DAD). The FT-IR spectra showed the presence of a large proportion of polyphenolic compounds, and the antioxidant analysis confirmed the antiradical activity. The control NPs showed less antiviral activity than the AuNPs-Sm and AgNPs-Sm, which was statistically significant; this demonstrates that both theS. mammosumextract and its corresponding NPs have a greater antiviral effect on the surrogate Phi bacteriophage, which is an appropriate model for studying SARS-CoV-2.
Assuntos
COVID-19 , Nanopartículas Metálicas , Solanum , Humanos , Nanopartículas Metálicas/química , Ouro/farmacologia , Ouro/química , SARS-CoV-2 , Espectroscopia de Infravermelho com Transformada de Fourier , Prata/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
Peptide engineering has gained attraction as a source of new cationicity-enhanced analogues with high potential for the design of next-generation antibiotics. In this context, cruzioseptin-1 (CZS-1), a peptide identified from Cruziohyla calcarifer, is recognized for its antimicrobial potency. However, this amidated-peptide is moderately hemolytic. In order to reduce toxicity and increase antimicrobial potency, 3 peptide analogues based on cruzioseptin-1 were designed and evaluated. [K4K15]CZS-1, an analogue with increased cationicity and reduced hydrophobicity, showed antibacterial, antifungal and antiproliferative properties. In addition, [K4K15]CZS-1 is less hemolytic than CZS-1. The in silico and scanning electron microscopy analysis reveal that [K4K15]CZS-1 induces a membranolytic effect on bacteria. Overall, these results confirm the potential of CZS-1 as source of inspiration for design new selective antimicrobial analogues useful for development of new therapeutic agents.