Folic acid-doxorubicin polymeric nanocapsules: A promising formulation for the treatment of triple-negative breast cancer

Author(s)

Ce, Rodrigo ^[1] ; Couto, Gabriela Klein ^[2] ; Pacheco, Barbara Zoche ^[3] ; Dallemole, Danieli Rosane ^[1] ; Paschoal, Julia Dame ^[2] ; Pacheco, Bruna Silveira ^[2] ; Guterres, Silvia Staniscuaski ^[1] ; Seixas, Fabiana ^[2] ; Collares, Tiago ^[2] ; Pohlmann, Adriana Raffin ^{[1, 3]}

Affiliation

^[1] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[2] Univ Fed Pelotas, Lab Biotecnol Canc, Grp Pesquisa Oncol Celular & Mol, Programa Posgrad Biotecnol, Biotecnol Ctr Desenvol, Pelotas, RS - Brazil

^[3] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, Av Bento Gonsalves 9500, BR-91501970 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 165, OCT 1 2021.
• Web of Science Citations: 0

Abstract

Breast cancer is the most common cancers among women and is one of the main causes of morbidity and mortality in this population. In this study, we aimed to conjugate doxorubicin (DOX), a drug widely used in cancer chemotherapy, and folic acid (FA), a ligand targeted for cancer therapy, to lipid-core nanocapsules (LNC), and evaluate the efficacy of the nanoformulation against triple-negative breast cancer (TNBC) MDA-MB-231 cells that overexpress folate receptors (FRs). We performed cell viability assays, quantitative real-time PCR (qRTPCR), cell migration assay, and clonogenic assay, as well as measured the levels of nitric oxide (NO) generated and cellular uptake. The results showed that the nanoformulation reduced cell viability. The results of qRT-PCR analysis revealed that the nanoformulation induced apoptosis of MDA-MB-231 cells. The mRNA expression levels of Cat and MnSod were increased when the nanoformulation was compared to the doxorubicin solution. Furthermore, the nanoformulation significantly decreased the migration of breast cancer cells in vitro and inhibited colony formation. Additionally, the expression of iNOS in MDA-MB-231 cells was higher when the nanoformulation was used compared to the doxorubicin solution. Cellular uptake was observed after incubating the MDA-MB-231 cells with the fluorescent-labeled nanoformulation. In conclusion, we developed a promising nanoformulation for the treatment of TNBC. Further studies are necessary to demonstrate the in vivo efficacy of this formulation. (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