No abstract

The effects of indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, or FFC14A), the second ruthenium compound that entered clinical trials, in an in vitro model of tumour invasion and metastasis show that the antitumour effects of this compound might include also the modulation of cell behaviour although its cytotoxicity appears to be predominant over these effects. The comparison with its imidazole analogue KP418 shows however its superiority, being able to control in vitro cell growth and in some instances also in vivo tumour development. These results suggest that the activity of KP1019 is predominantly due to direct cytotoxic effects for tumour cells, evident also in vivo on primary tumour growth and that the effects on modulation of the biological behaviour of the cancer cell can be present but might have only a partial role.

Regenerative medicine is continuously facing new challenges and it is searching for new biocompatible, green/natural polymer materials, possibly biodegradable and non-immunogenic. Moreover, the critical importance of the nano/microstructuring of surfaces is overall accepted for their full biocompatibility and in vitro/in vivo performances. Chitosan is emerging as a promising biopolymer for tissue engineering and its application can be further improved by exploiting its nano/microstructuration. Here, we report the state of the art of chitosan films and scaffolds nano/micro-structuration. We show that it is possible to obtain, by solvent casting, chitosan thin films with good mechanical properties and to structure them at the microscale and even nanoscale level, with resolutions down to 100 nm.

Peripheral nerve injuries are a common condition in which a nerve is damaged, affecting more than one million people every year. There are still no efficient therapeutic treatments for these injuries. Artificial scaffolds can offer new opportunities for nerve regeneration applications; in this framework, chitosan is emerging as a promising biomaterial. Here, we set up a simple and effective method for the production of micro-structured chitosan films by solvent casting, with high fidelity in the micro-pattern reproducibility. Three types of chitosan directional micro-grooved patterns, presenting different levels of symmetricity, were developed for application in nerve regenerative medicine: gratings (GR), isosceles triangles (ISO) and scalene triangles (SCA). The directional patterns were tested with a Schwann cell line. The most asymmetric topography (SCA), although it polarized the cell shaping less efficiently, promoted higher cell proliferation and a faster cell migration, both individually and collectively, with a higher directional persistence of motion. Overall, the use of micro-structured asymmetrical directional topographies may be exploited to enhance the nerve regeneration process mediated by chitosan scaffolds.

The ruthenium-based drug NAMI-A, characterised by its selectivity against solid tumour metastases, promotes TGF-β1-dependent fibrosis and the reduction of the release of MMPs in the primary tumour. The aim of the study was to examine the interaction of NAMI-A with TGF-β1 in the process of metastasis formation. NAMI-A (1) affects the secretion of TGF-β1 in metastatic MDA-MB-231 cells rather than in non-tumorigenic HBL-100 cells, (2) prevails over TGF-β1 with regard to the invasive capacity of the treated cells, and (3) contrasts integrin-dependent migration stimulated by TGF-β1. It, thus, appears that the effects of NAMI-A on cell invasion and migration are best summarised as an interference with TGF-β1 and a reduction of its activity in these events. At a molecular level, the similar activity of NAMI-A and TGF-β1 on RhoA GTPase supports its interaction with cell surface integrins while TGF-β1 can activate it by interaction with its TGFβR receptor. The inhibition of TGF-β1-induced migration of MDA-MB-231 cells by NAMI-A cannot simply be attributed to a modulation of the Smad2 and p38MAPK pathways. In conclusion, the effects of NAMI-A on the biological role of TGF-β1 in cancer metastasis are insufficient to attribute the responsibility for the anti-metastatic activity of the ruthenium-based drug to this target alone.