Tretinoin-loaded lipid-core nanocapsules overcome the triple-negative breast cancer cell resistance to tretinoin and show synergistic effect on cytotoxicity induced by doxorubicin and 5-fluororacil

Author(s)

Schultze, Eduarda ^[1] ; Buss, Julieti ^[1] ; Coradini, Karine ^[2] ; Begnini, Karine Rech ^[1] ; Guterres, Silvia S. ^{[3, 2]} ; Collares, Tiago ^[1] ; Ruver Beck, Ruy Carlos ^{[3, 2]} ; Pohlmann, Adriana R. ^{[3, 2, 4]} ; Seixas, Fabiana Kommling ^[1]

Affiliation

^[1] Univ Fed Pelotas, Biotecnol Ctr Desenvolvimento Tecnol, Lab Biotecnol Canc, Grp Pesquisa Oncol Celular & Mol, PPGB, Pelotas, RS - Brazil

^[2] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Nanotecnol Farmaceut, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[4] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, PBox 15003, BR-91501970 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 96, p. 404-409, DEC 2017.
• Web of Science Citations: 8

Abstract

Nanostructured drug delivery systems have been extensively studied, mainly for applications in cancer therapy. The advantages of these materials include protection against drug degradation and improvement in both the relative solubility of poorly water soluble drugs as in targeting of therapy, due to the enhanced permeability and retention effect on tumor sites. In this work, we evaluate the antitumor activity of tretinoin-loaded lipid core nanocapsules (TT-LNC) in a tretinoin-resistant breast cancer cell-line, MDA-MB-231, as well as the synergistic effect of combination of this treatment with 5-FU or DOXO. The inhibition of cell growth was assayed by MTT reduction. Live/Dead assay and DAPI staining evaluated cytotoxicity. Apoptosis was evaluated by Annexin V-PE/7AAD and the effect of chronic exposure was evaluated by colony formation assay. TT-LNC reduced the cell viability even at lower concentrations (1 mu M) and displayed synergistic effect with 5-FU or DOXO on cytotoxicity and colony formation inhibition. Our work shows a possibility of using nanocapsules to improve the antitumoral activity of TT for its use either alone or in combination with other chemotherapeutic drugs, especially considering the chronic effect. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants