pH sensitive functionalized graphene oxide for the release of drugs

A facile strategy of polyacrylate (PAA) grafting was used to develop a pH stimuli-responsive theranostic platform based on graphene oxide (GO) nanosheets of homogeneous size. Indeed, the GO lateral size was found to signi[cantly affect its surface charge, optical properties as well as the cellular uptake. The actual surface termination of the GO/polymer hybrid, prepared at two different acrylate grafting ratios, was scrutinised by a multitechnique approach, including spectroscopic (UV-visible, euorescence, Raman, ATR-FTIR, XPS), spectrometric (ToF-SIMS and –for the [rst time- ESI-MS) and microscopic (AFM, confocal microscopy) methods. Atomistic Molecular Dynamics (MD) simulations of both the physisorption process and the hydration behaviour of the aggregate consisting of gemcitabine (GEM) - (PAA) - (GO) are performed in explicit solvent medium at two different pH values. The different ionization of pH sensitive groups characterizing the aggregate ineuences the energy of physisorption and the hydration shell around the complex. The decrease of negative charge density, occurring at acid pH, facilitates the physisorption process between PAA and GO. On the other hand, at the same pH value, a weaker interaction between GEM and PAA is observed. MD simulations show a partial physisorption of the drug from the polymer at pH = 4.0. pH change affects also morphology of GO sheet which is more extended at basic pH value due to intrasheet electrostatic interactions. Radial distribution function (RDF) indicates that carboxylate oxygens of PAA and alkoxide oxygens of GO strongly attract dipolar water molecules, thus affecting the hydration shell around the complex in comparison with unionized GO and bulk water. Finally, an analysis based on H-bond correlation function clearly shows that: a) hydrogen bond between both carboxylate and alkoxide oxygen atoms are longer lived than those observed in unionized GO and bulk water; b) RDF decays slower for PAA (f = 0.8) with respect to ionized GO, hence indicating that COO- groups bind water molecules stronger than R-O-.