Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes’ inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response

Regeneration and DNA methylation do not trigger PDX-1 expression in rat liver

IN PRES

Acute ocular hypertension as a model retinal cell degeneration

Sono stati studiati gli effetti dell’ipertensione oculare sperimentale sulle cellule retiniche. Sono stati valutati i livelli della pressione intraoculare ed il grado di danneggiamento delle cellule mediante l’analisi citochimica e del DNA. I dati dimostrano che l’ipertensione oculare acuta causa una estesa morte delle cellule retiniche per apoptosi

Apoptotic degeneration induction in retinal cells by acute ocular hypertension and neuroprotection by troxol

The effects of acute experimental ocular hypertension on retinal cells have been studied. IOP levels and degree of cell damage have been evaluated by cytochemical and DNA analysis, by which the degeneration, necrotic and apoptotic modalities were observed. Possible pharmacological approaches, e.g. neuroprotection with troxol, have been determined for the prevention of the degenerative events that may be ascribed, at least in part, to oxidizing processe

Effect of whole body hyperthermic sessions on the heat shock response in mice liver and brain

We examined by Western blots the effect of variations of the heating sessions, such as duration and intensity on the following aspects: 70-kDa heat shock protein (HSP70) and HSP72 induction. Protein ubiquitination PLC gamma PKC epsilon and PKC alpha levels in murine liver and brain were also studied. Results demonstrated that maximal induction of HSP72 was obtained after heat shock at 43.5 degrees C in both organs. Preconditioning at lower temperatures (either acclimation to 39 degrees C or induction of thermotolerance to 43.5 degrees C with a single exposure to 39 degrees C) attenuated the heat shock response. Hepatic HSP72 induction was elicited only as a consequence of hyperthermia since either fasting or restraint were unable to trigger its synthesis. On the contrary, a ubiquitination decrease of a 31 kDa protein was obtained both after hyperthermia and fasting This indicates that the latter is a more generic response of hepatic cells to noxious stimuli. Analysis of the above mentioned enzymes showed that in liver of naive mice PKC alpha is barely present while PKC epsilon is quite abundant. All hyperthermic treatments caused a general decrease of the latter, except for the heat shock at 43.5 degrees C that caused an increase. PLC gamma decreased after all heating sessions. It is known that hyperthermia in the range of 41-45 degrees C induces apoptotic death in many cell types. Therefore we analyzed the presence of the typical apoptotic DNA ladder. Our data strongly suggest that both hyperthermia and restraint induce necrosis in liver while apoptosis and necrosis become evident in brain. All these effects are still present 24 h from the last heating session: This indicates that in vivo, hyperthermia produces long term modifications of the hepatic cell

“Effetto di xenobiotici sulla proliferazione cellulare: meccanismi cellulari e molecolari”

Quando l'omeostasi cellulare viene turbata, la cellula subisce uno stress che può modificare la proliferazione e la morte cellulare. Tale equilibrio viene continuamente modificato dal contatto che le cellule e gli organismi hanno con farmaci, sostanze naturali o prodotte da processi industriali. I meccanismi con cui le cellule rispondono alle interazioni con tale sostanze e gli effetti da esse prodotti sono oggetto di ricerca in varie discipline. Ilpresente programma intende studiare questi meccanismi utilizzando sistemi ed approcci sperimentali diversi

Induced acute ocular hypertension: mode of of retinal degeneration

The effects of experimental hypertension on retinal cells were studied. Evaluation was made of IOP levels and degree of cell damage by cytochemical and DNA analysis, and degeneration modes: necrosis and apoptosis