4.6 Article

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

期刊

出版社

ELSEVIER
DOI: 10.1016/j.ejps.2021.105943

关键词

Breast cancer; MDA-MB-231; folic acid; nanocapsules; doxorubicin; folate receptors

资金

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]
  2. Sao Paulo Research Foundation (FAPESP, Brazil) [2014/50928-2]
  3. National Council of Technological and Scientific Development (CNPq, Brazil) [465687/2014-8]
  4. Research Support Foundation of the State of Rio Grande do Sul in Brazil [FAPERGS 12/2014: PRONEX FAPERGS/CNPq, 16/2551-0000467-6, 17/2551-0001002-7]

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The study developed a promising nanoformulation for the treatment of triple-negative breast cancer (TNBC), showing effectiveness in reducing cell viability, inducing apoptosis, inhibiting cell migration, and colony formation in breast cancer cells. Further studies are needed to demonstrate the in vivo efficacy of this formulation.
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.

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