Breast cancer is the type of
cancer with the highest incidence in women around the world. Noteworthy, the triple-negative subtype affects 20% of the patients while presenting the highest death rate among subtypes. This is due to its aggressive phenotype and the capability of invading other tissues. In general, tumor-associated macrophages (TAM) and other immune cells, are responsible for maintaining a favorable tumor microenvironment for
inflammation and
metastasis by secreting several mediators such as pro-inflammatory
cytokines IL-1β,
IL-6, and TNF-α,
chemokines like CCL2, and other
proteins, as
metalloproteinases of matrix (
MMP). On the other hand,
immunomodulatory agents can interfere in the immune response of TAM and change the disease prognosis. In this work, we prepared nanostructured
lipid carriers containing
kaurenoic acid (NLC-KA) to evaluate the effect on
cytokine production in vitro of bone marrow-derived macrophages (BMDM) and the migratory process of 4 T1
breast cancer cells. NLC-KA prepared from a blend of natural
lipids was shown to have approximately 90 nm in diameter with low polydispersity index. To test the effect on
cytokine production in vitro in NLC-KA treated BMDM, ELISA assay was performed and pro-inflammatory
cytokines IL-1β,
IL-6, and TNF-α were quantified. The formulation reduced the secretion of IL-1β and TNF-α
cytokines while presenting no hemolytic activity. Noteworthy, an anti-migratory effect in 4 T1
breast cancer cells treated with NLC-KA was observed in scratch assays. Further, MMP9 and CCL2 gene expressions in both BMDM and 4 T1 treated cells confirmed that the mechanism of inhibition of migration is related to the blockade of this pathway by KA. Finally, cell invasion assays confirmed that NLC-KA treatment resulted in less invasiveness of 4 T1 cells than control, and it is independent of CCL2 stimulus or BMDM direct stimulus. Ultimately, NLC-KA was able to regulate the
cytokine production in vitro and reduce the migration of 4 T1
breast cancer cells by decreasing MMP9 gene expression.