Tiziana Fiore

Ferulic acid, a natural phenolic phytotherapeutic, which is mainly found in plant cell walls, has attracted the attention of researchers for its multiple pharmacological properties, especially for its anti-tumor potential. As an efficient antioxidant, the compound counteracts oxidative stress and modulates key molecular pathways involved in carcinogenesis. Recent studies demonstrate that ferulic acid exerts antiproliferative, pro-apoptotic, and anti-metastatic effects in various tumor models, including colon, breast, liver, and lung cancers. Mechanistically, ferulic acid affects components of prosurvival-signaling pathways such as PI3K/Akt, MAPK, and NF-κB, and stimulates programmed cell death by diverse mechanisms, including apoptosis, autophagy and ferroptosis. Furthermore, its ability to sensitize cancer cells to chemotherapeutic drugs with low toxicity to normal cells underscores its therapeutic potential. Despite promising preclinical anti-tumor activity, low water solubility and bioavailability limit its clinical use. For this reason, several attempts, ranging from chemical derivatives to nanodevices, have been made to improve ferulic bioavailability and anti-tumor efficacy. This review highlights the most significant and recent strategies to ameliorate the anticancer ability of ferulic acid in the perspective of a clinical application.

Stimuli-responsive smart microrobots perform “on-demand” and highly efficient decontamination of polluted sites.

Combining biologically active compounds with nanocarriers is an emerging and promising strategy for enhancing the activities of molecules while reducing their levels of toxicity. Green nanomaterials have recently gained momentum in developing protocols for treating and preserving artifacts. In this study, we designed a functional biohybrid material by incorporating tributyltin(IV) ferulate (TBT-F) into halloysite nanotubes (HNTs), generating a new formulation called HNT/TBT-F. The primary objective was to develop a formulation with robust antimicrobial properties and reinforcing features for treating paper with artistic and historical value. To characterize HNT/TBT-F, assess the HNT’s loading capacity, and investigate the TBT-F release kinetics from the nanotubes, various analytical techniques, including UV-Vis and infrared spectroscopies, thermogravimetry, and microscopy analysis, were employed. Furthermore, we evaluated the antimicrobial potential of TBT-F and HNT/TBT-F against Kocuria rhizophila, a bacterial strain known for its opportunistic behavior and a cause of artifact biodeterioration. HNT/TBT-F exhibited a significantly stronger bactericidal effect than TBT-F alone against K. rhizophila cells growing planktonically or those forming a biofilm. This enhanced performance could relate to the confinement of TBT-F within the nanotubes, which likely improved its physical-chemical stability and increased the local concentration of TBT-F upon contact with the bacterial cells. Additionally, we evaluated the mechanical properties of a paper treated with HNT/TBT-F, assessing any potential alterations in its color. The findings of this study highlight the favorable attributes of the HNT/TBT-F formulation and its potential for developing protocols aimed at consolidating and preserving culturally significant paper objects.

Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (¹H, ¹³C and ¹¹⁹Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 μM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.

Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment.

Melanoma is the most aggressive and deadly form of skin cancer, which is largely due to its propensity to metastasize. Therefore, with the aim to inhibit the growth and the metastatic dissemination of melanoma cells and to provide a novel treatment option, we studied the effects of the melanoma treatment with two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, namely (Bu₂Sn)₂TPPS and (Bu₃Sn)₄TPPS. In particular, we showed that nanomolar concentrations of (Bu₂Sn)₂TPPS and (Bu₃Sn)₄TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of the full-length poly (ADP-ribose) polymerase (PARP-1), to induce the cell cycle arrest respectively at G2/M and G0/G1 through the inhibition of the Cyclin D1 expression and to inhibit cell colony formation. Nanomolar concentrations of (Bu₂Sn)₂TPPS and (Bu₃Sn)₄TPPS are also sufficient to inhibit the melanoma cell migration and the expression of some adhesion receptors. Moreover, we report that (Bu₂Sn)₂TPPS and (Bu₃Sn)₄TPPS act downstream of BRAF, mainly bypassing its functions, but targeting the STAT3 signalling protein. Finally, these results suggest that (Bu₂Sn)₂TPPS and (Bu₃Sn)₄TPPS may be effective therapeutic strategies for their role in the inhibition of melanoma growth and migration.

Semitransparent perovskite solar cells (ST‐PSCs) are highly attractive for applications in building‐integrated photovoltaics as well as in multijunction tandem devices. To fabricate high‐performance ST‐PSCs, suitable transparent top electrodes are strongly needed. Dielectric/metal/dielectric (DMD) multilayer structures have been shown to be promising candidates, though generally based on high‐value metals such as gold or silver, the latter causing also stability issues by reacting with perovskite. Here, a novel DMD transparent electrode based on nonprecious, less‐reactive copper is developed via thermal evaporation and used as a top anode in the fabrication of high‐performance semitransparent n‐i‐p perovskite solar cells, the best device yielding a power conversion efficiency as high as 12.5%. The DMD architecture consists of a gold‐seeded Cu thin film sandwiched between two MoO _x dielectric layers. It is demonstrated that Cu self‐aggregation and diffusion into MoO_x can be substantially limited by introducing an ultrathin (1.5 nm) Au seed layer, and conductive Cu films as thin as 9.5 nm can be achieved. A fine tuning of the perovskite layer thickness is also carried out to further enhance the device transparency up to a maximum average visible transmittance approaching 25%.

Enhancement of luminescence efficiency caused by interaction of H⁺ ions with nonradiative defects at the SiNC/SiO₂ interface.