Assessment of seriniquinone delivery to melanoma cells by poly (D,L-lactic-co-glycolic) acid (PLGA) nanoparticles

• Grant number: 22/15832-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Leticia Veras Costa Lotufo
• Grantee: Rodrigo dos Anjos Miguel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM
• Associated scholarship(s): 23/17281-4 - Understanding the role of dermcidin on melanoma survival and migration using seriniquinone as a pharmacological tool, BE.EP.MS

Abstract

Seriniquinone (SQ) and its derivatives comprise a group of substances with potent cytotoxic activity, showing selectivity for melanoma cell lines. These substances have presented a novel and distinct mechanism of action when compared to other quinones, through binding to dermcidin (DCD) and triggering autophagocytosis and apoptosis. One of the challenges for the advancement of SQ in the studies of its anticancer properties is its low solubility in water, stimulating the development of formulations based on its encapsulation in poly (D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs) for its dispersion in aqueous vehicles. The developed PLGA-NPs have demonstrated ideal characteristics for administration and maintenance of activity with encapsulation. Therefore, with the present project, our aim is to understand cell-nanocarrier interactions, to use more robust in vitro models and to verify the maintenance of SQ-DCD interaction, its molecular target, with nanoencapsulation. To observe internalization and intracellular trafficking of NPs, it is proposed to use flow cytometry and confocal microscopy. To mimic the tumor microenvironment, melanoma spheroid models, and in co-culture with fibroblasts and macrophages, will be used for evaluation of cytotoxicity and penetration of NPs by confocal microscopy. To assess cytotoxicity and inhibition of tumoral proliferation and invasiveness, staining with hematoxylin and eosin (H&E) will be performed for histological sections of reconstituted human skin in vitro model after treatment. To verify the maintenance of the interaction with DCD after encapsulation, RT-qPCR and Western blot techniques will be used to analyze the gene and protein modulation.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MIGUEL, RODRIGO DOS A.; HIRATA, AMANDA S.; SALATA, GIOVANNA C.; APOLINARIO, ALEXSANDRA C.; BARROSO, VINICIUS M.; ISHIDA, KELLY; CLAIR, JAMES J. LA; FENICAL, WILLIAM; MARTINS, TEREZA S.; COSTA-LOTUFO, LETICIA V.; et al. Topical delivery of seriniquinone for treatment of skin cancer and fungal infections is enabled by a liquid crystalline lamellar phase. European Journal of Pharmaceutical Sciences, v. 192, p. 14-pg., 2023-11-24. (22/15832-0, 18/11612-0, 18/13877-1, 20/09270-4, 20/06613-8, 19/26048-6, 22/05133-8, 15/17177-6, 19/08582-5, 21/01279-5)