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Jorge, Genesy Perez ; Gontijo, Marco ; Floro e Silva, Marina ; Liszbinski, Raquel Bester ; Tavares, Renata Spagolla Napoleao ; von Zuben de Valega Negrao, Cyro ; Oliveira Grundmann, Carlismari ; Goes, Isabella Carolina Rodrigues dos Santos ; Coser, Lilian de Oliveira ; Bilsland, Elizabeth ; Rocha, Francisca Janaina Soares ; Pupo, Monica Tallarico ; Giorgio, Selma ; Dias, Sandra Martha Gomes ; Almeida, Fausto ; Brocchi, Marcelo

• Tipo de documento: Artigo Científico
• Fonte: ACS BIOMATERIALS SCIENCE & ENGINEERING; v. 11, n. 10, p. 19-pg., 2025-09-11.

Resumo

Violacein exhibits antitumor activity, indicating potential for future clinical application. However, an efficient delivery system is required for the clinical use of this hydrophobic compound. Effective delivery systems can enhance the solubility and bioavailability of hydrophobic compounds like violacein, facilitating its clinical application for antitumor therapy. Recent studies have demonstrated that outer membrane vesicles (OMVs) can serve as nanocarriers. This article constitutes the first report to present both in vivo and in vitro investigations of OMVs derived from a hypervesiculating mutant of Salmonella enterica Typhimurium as a delivery vehicle for violacein. In this study, S. enterica Typhimurium Delta tolRA (with a hypervesiculated phenotype) was transformed with a plasmid encoding the violacein biosynthesis operon. OMVs and violacein-loaded OMVs were isolated, characterized, and used in the treatment of murine melanoma. We assessed the cytotoxic effect of these violacein-loaded OMVs in both two-dimensional (2D) and three-dimensional (3D) cell cultures. Violacein-loaded OMVs reduced melanoma cell viability (IC50: 9.30 x 108 vesicles/mL) and delivered violacein in melanoma cells. Additionally, tumor regression was associated with treating tumor-bearing mice with violacein-loaded OMVs or nonviolacein-loaded OMVs (5 x 109 vesicles/mouse). The antitumor response was linked to the accumulation of M1-type macrophages in the tumor microenvironment and the overexpression of mRNA for antitumor mediators Inducible Nitric Oxide Synthase, Tumor Necrosis Factor-alpha, and Interleukin-6 (iNOS, TNF-alpha, and IL-6). Our results suggest that OMVs can act as nanocarriers for highly hydrophobic agents and induce antitumor responses to eliminate tumors. (AU)

• Processo FAPESP: 21/00465-0 - Genômica, patogenicidade, resistência, terapia antitumoral e vacinas baseadas em Salmonella enterica
• Beneficiário: Marcelo Brocchi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/17091-5 - Análise fenotípica de macrófagos e histopatologia em camundongos infectados com Leishmania braziliensis
• Beneficiário: Marina Flóro e Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 22/11399-0 - Salmonella enterica e Vesículas de Membrana Externa Como Agente Antitumoral
• Beneficiário: Genesy Perez Jorge
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 21/10577-0 - Centro de Pesquisa em Biologia de Bactérias e Bacteriófagos (CEPID B3)
• Beneficiário: Shaker Chuck Farah
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 23/03213-7 - Salmonella enterica e Vesículas de Membrana (MVs) no Desenvolvimento de Vacinas
• Beneficiário: Marina Flóro e Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 20/06430-0 - Combinando métodos modernos de espectrometria de massas e genome mining para a análise de interações entre microrganismos simbiontes de colônias de Trachymyrmex
• Beneficiário: Carlismari Oliveira Grundmann
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/01535-9 - Genômica comparativa e atividade antimicrobiana de endolisinas fágicas recombinantes contra bactérias gram-negativas multirresistentes
• Beneficiário: Marco Túlio Pardini Gontijo
• Modalidade de apoio: Bolsas no Brasil - Mestrado