Triple negative breast cancer (TNBC) is a highly aggressive, invasive, and metastatic tumor. Although it is reported to be sensitive to cytotoxic chemotherapeutics, frequent relapse and chemoresistance often result in treatment failure. In this study, we developed a biomimetic nanodrug consisting of a self-assembling variant (HFn) of human apoferritin loaded with curcumin. HFn nanocage improved the solubility, chemical stability, and bioavailability of curcumin, allowing us to reliably carry out several experiments in the attempt to establish the potential of this molecule as a therapeutic agent and elucidate the mechanism of action in TNBC. HFn biopolymer was designed to bind selectively to the TfR1 receptor overexpressed in TNBC cells. HFn-curcumin (CFn) proved to be more effective in viability assays compared to the drug alone using MDA-MB-468 and MDA-MB-231 cell lines, representative of basal and claudin-low TNBC subtypes, respectively. Cellular uptake of CFn was demonstrated by flow cytometry and label-free confocal Raman imaging. CFn could act as a chemosensitizer enhancing the cytotoxic effect of doxorubicin by interfering with the activity of multidrug resistance transporters. In addition, CFn exhibited different cell cycle effects on these two TNBC cell lines, blocking MDA-MB-231 in G0/G1 phase, whereas MDA-MB-468 accumulated in G2/M phase. CFn was able to inhibit the Akt phosphorylation, suggesting that the effect on the proliferation and cell cycle involved the alteration of PI3K/Akt pathway.

The aim of the present work was to study the in vivo anti-inflammatory activity of six NSAIDs, ibuprofen, diclofenac, nimesulide, meloxicam, celecoxib and rofecoxib, using the rat air-pouch model of inflammation to characterize the ability of these drugs to induce gastric damage and PGE(2) inhibition. Selective compounds were observed to have no ulcerogenic properties at anti-inflammatory doses; however, these drugs were weaker inhibitors of several inflammatory aspects such as cell influx and exudate formation. In contrast, the non-selective and preferential compounds present anti-inflammatory properties at lower doses than presented by selective drugs. At anti-inflammatory doses, only meloxicam and ibuprofen produced gastric damage and inhibition of PGE(2) synthesis, suggesting that ulcerogenic properties of NSAIDs cannot be predicted by their selectivity index, since meloxicam demonstrates ulcerogenic properties despite its preferential profile.