RESUMEN

Gold nanoparticles functionalized with doxorubicin and stabilized with multilayers of degradable polyelectrolyte were allowed to age in aqueous medium in vitro in order to show the possibility of drug release in cellular environment. The chemico-physical characteristics of the nanoparticles are reported. The observed release of doxorubicin (DOX) was pH-dependent, and it increased in acidic environment. Cell uptake of nanoparticles and drug release were monitored by laser scanning confocal microscopy. Data showed that drug-bearing nanoparticles delivered DOX into the nuclei of A549 cells, leading to pronounced cytotoxic effects to this lung tumor cells. Our results suggest that gold nanoparticles conjugated with doxorubicin could be used as a pH-triggered drug releasing carrier for tumor drug delivery.

Asunto(s)

Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas del Metal/química , Adsorción , Antibióticos Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Doxorrubicina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Oro/química , Humanos , Nanopartículas del Metal/administración & dosificación , Poliaminas/química , Polilisina/análogos & derivados , Polilisina/química

RESUMEN

Staphylococcal leucotoxins result from the association of class S components and class F component inducing the activation and the permeabilization of the target cells. Like alpha-toxin, the leucotoxins are pore-forming toxins with more than 70% beta-sheet. This was confirmed by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. In addition, threonine 28 of a predicted and conserved beta-sheet at the N-terminal extremity of class S proteins composing leucotoxins aligns with histidine 35 of alpha-toxin, which has a key role in oligomerization of the final pore. Flow cytometry was used to study different aminoacid substitutions of the threonine 28 in order to evaluate its role in the biological activity of these class S proteins. Finally, results show that threonine 28 of the leucotoxin probably plays a role similar to that of histidine 35 of alpha-toxin. Mutations on this threonin largely influenced the secondary interaction of the class F component and led to inactive toxin.