MoS2 flakes stabilized with DNA/RNA nucleotides: in vitro cell response

Two-dimensional transition metal dichalcogenides (TMDCs), such as MoS2 and WS2, have recently emerged as nanomaterials with potential use in biomedicine. An attractive means to favor their interaction with biological media is the use of proper biomolecules as exfoliating/dispersing agents. Here, MoS2 flakes were stabilized with different small functional biomolecules such as adenosine monophosphate (AMP), guanosine monophosphate (GMP) and flavin mononucleotide (FMN) through the strong nucleotide-MoS2 interaction of Lewis acid-base type, rather than just on the weak dispersive and hydrophobic forces commonly associated with the use of many surfactants. The impact of the nucleotide-stabilized MoS2 flakes on the viability and cell proliferation, on the production of intracellular reactive oxygen species (ROS), and on the preosteoblast differentiation process (early stage) has been also evaluated, as well as the incorporation and intracellular localization of the nanomaterials by MC3T3-E1 and Saos-2 cells. The nucleotide-stabilized MoS2 flakes were found to exhibit excellent biocompatibility. Furthermore, their incorporation did not affect the integrity of the cell plasma membrane, which makes them ideal candidates for delivering drug/gene directly into cells. The in vitro cell response of tumor cells to these nanomaterials differs from that of undifferentiated cells, which provides the basis for their potential use in cancer therapy.publishe

An in vitro biofilm model of Staphylococcus aureus infection of bone

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an invitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72h biofilms with gentamicin and daptomycin for 24h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100mgl−1 gentamicin and 1000mg l−1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7days resulted in ≥3 log reductions in cell numbers by 48h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. Significance and Impact of the Study: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an invitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis