Assessment of Cytotoxicity of Gold Nanoparticles Functionalized With Brazilian Red Propolis in 2D And 3D Models of Urological Cancers
Notice bibliographique
Résumé
The major urological cancers are prostate adenocarcinoma and urinary bladder [1].Prostate cancer (PCa) and Bladder cancer (BC) are, respectively, the second and the sixth most frequently diagnosed cancer among men worldwide [2], [3].Innovative clinical approaches that could result in more effective treatment options, such as gold nanoparticles (AuNPs) functionalized with natural compounds could be offer advantages such as increased efficacy and reduced systemic cytotoxicity [4].Brazilian red propolis (BRP) is a natural product known for its anti-inflammatory, antioxidant and antitumor properties [5].In this way, the aims of our research were the development of a therapeutic formulation composed of AuNPs functionalized with BRP and the investigation of their biological activities against urological cancers.Through a green synthesis method, AuNPs were produced using the crude extract of BRP for reducing Au +3 to Au 0 .The dispersion color changed from pale yellow to dark red indicating the production of BRP-AuNPs, which was also confirmed by the formation of a surface plasmon resonance band (SPR band) around 535 nm by UV-VIS Spectrophotometry.Green synthesized AuNPs (BRP-AuNPs) were characterized about hydrodynamic diameter and Polydispersity Index (PDI) by Dynamic Light Scattering (DLS), which demonstrated a monomodal distribution.Zeta Potential value measured by electrophoretic light scattering was negative.Further characterizations were given by Nanoparticle Tracking Analysis (NTA) showing a concentration of nanoparticles of 1,49 x10 10 particles/mL.Moreover, AuNPs were analyzed by Transmission Electron Microscopy (TEM) showing predominantly spherical morphology and size in the range of 2-15 nm.Biological studies were performed to investigate the activity of these nanoparticles against urological cancer cells.Cytotoxicity assays using PC3 (prostate cancer) and RT4 (bladder cancer) cell lines revealed that both BRP extract and BRP-AuNPs exhibited a dose dependent antitumor effect.The IC50 values of BRP extract were 58 µg/mL (RT4) and 21.8 µg/mL (PC3), while BRP-AuNPs IC50 values were 27.32 µg/mL (RT4) and 53 µg/mL (PC3).These results suggest higher cytotoxic activity of BRP extract when it compared with BRP-AuNPs.Besides that, BRP-AuNPs demonstrated good ability to kill cancer cells.These data were also confirmed by ATP bioluminescence and flow cytometry studies, which indicated a percentage of apoptosis around 44-66%.Further investigations were performed in urological cancer 3D models.For this, PC3 and RT4 spheroids were treated with BRP extract and nanoparticles dispersion.The cytotoxic activity was investigated by ATP luminescence measurement and also by spheroid images taken before and after the treatment.From these assays, interesting results were acquired, revealing an opposite effect of that demonstrated by 2D viability assays.In 3D viability assays a superior antitumor effect of BRP-AuNPs were exhibited when compared with free BRP extract.These data suggest that nanoparticles are able to penetrate deeper inside the spheroids than the natural compounds, due to their small size.Moreover, live and dead cells in the spheroids were visualized by confocal microscopy after viability dyes staining.Therefore, our research data have demonstrated that gold nanoparticles were synthesized from Brazilian red propolis by the green synthesis method and also exhibited interesting biological activities against urological cancers, being a potential antitumor formulation.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».