Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were...

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Published in:Artificial cells, nanomedicine, and biotechnology nanomedicine, and biotechnology, 2020-01, Vol.48 (1), p.515-524
Main Authors: Bonfim, Caroline Measso do, Monteleoni, Letícia Figueiredo, Calmon, Marília de Freitas, Cândido, Natália Maria, Provazzi, Paola Jocelan Scarin, Lino, Vanesca de Souza, Rabachini, Tatiana, Sichero, Laura, Villa, Luisa Lina, Quintana, Silvana Maria, Melli, Patrícia Pereira dos Santos, Primo, Fernando Lucas, Amantino, Camila Fernanda, Tedesco, Antonio Claudio, Boccardo, Enrique, Rahal, Paula
Format: Article
Language:English
Subjects:
Antiviral activity
Apoptosis
Assaying
Bioactive compounds
Biocompatibility
Caspase-3
Cell death
Cell viability
Curcumin
curcumin and photodynamic therapy
Cytotoxicity
Drug delivery
Drug delivery systems
Emulsions
Enzymatic activity
HPV
Human papillomavirus
Irradiation
nanoemulsion
Nanoemulsions
Nanoparticles
Photoactivation
Photodynamic therapy
Polymorphism
Radiation
Restriction fragment length polymorphism
Toxicity
Vulva
Vulvar intraepithelial neoplasia
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Summary:Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.
ISSN:2169-1401
2169-141X
DOI:10.1080/21691401.2020.1725023