Band 9, Heft 2

Graphene oxide (GO) nanomaterials offer a wide range of bioimaging applicability. Almost complete quenching ability of fluorescence by GO and natural interaction of GO with single stranded nucleic acid made GO a useful and intriguing multifunctional nanoplatform both as a biosensor for in vitro microplate diagnostics and as a drug delivery carrier for targeted delivery. GO’s large surface area and strong near infrared absorbance contribute to enhancement of a therapeutic effect with abundant loading of drugs for possible photothermal and photodynamic therapy. Bioimaging capability of GO made it a good theranostic tool, while enabling tracing in vivo pharmacokinetics during concurrent treatment. Fluorescence, either signal on or off, Raman and surface-enhanced Raman scattering (SERs), photoacoustic, and radionuclide imaging modalities can be used for theranostic purposes using GO nanomaterials. In this review, we highlight current applications of GO for bioimaging that are classified into in vitro microplate, in vitro cellular and in vivo bioimaging.

Complement activation-related pseudoallergy (CARPA) is a hypersensitivity reaction occurring upon intravenous administration of numerous liposomal therapeutics, other nonbiological complex drugs and biologicals. It has a complex molecular and cellular mechanism that involves the production, actions and interactions of numerous vasoactive mediators in blood, including thromboxane A 2 (TXA 2 ). This short review focuses on the latter eicosanoid: its role in CARPA, effects underlying some of the symptoms and experimental evidence for its rate-limiting role in pulmonary hypertension in pigs. Animal experiments and recent clinical observations suggest that the cyclooxygenase blocker indomethacin may represent an effective new approach to prevent liposome-induced CARPA, lending clinical relevance to better understand the involvement of TXA2 and other eicosanoids in this adverse immune effect.

Polydimethylsiloxanes (PDMS) have drawn attention because of their applicability in medical implants, soft robotics and microfluidic devices. This article examines the formation of dedicated nanostructures on liquid submicrometer PDMS films when exposed to oxygen-plasma treatment. We show that by using a vinyl-terminated PDMS prepolymer with a molecular weight of 800 g/mol, one can bypass the need of solvent, copolymer, or catalyst to fabricate wrinkled films. The amplitude and periodicity of the wrinkles is tuned varying the thickness of the PDMS film between 150 and 600 nm. The duration of the plasma treatment and the oxygen pressure determine the surface morphology. The amplitude was found between 30 and 300 nm with periodicities ranging from 500 to 2800 nm. Atomic force microscopy was used to measure film thickness, amplitude and wrinkle periodicity. The hydrophobic recovery of the nanostructured PDMS surface, as assessed by dynamic contact angle measurements, scales with nanostructure’s fineness, associated with an improved biocompatibility. The mechanical properties were extracted out of 10,000 nanoindentations on 50×50-μm 2 spots. The mechanical mapping with sub-micrometer resolution reveals elastic properties according to the film morphology. Finally, we tailored the mechanical properties of a 590±120-nm-thin silicone film to the elastic modulus of several MPa, as required for dielectric elastomer actuators, to be used as artificial muscles for incontinence treatments.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been identified as a promising material for biomedical applications. These include as contrast agents for medical imaging, drug delivery and/or cancer cell treatment. The nanotoxicological profile of SPIONs has been investigated in different studies and the distribution of SPIONs in the human body has not been fully characterized. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to predict the pharmacokinetics of SPIONs. The distribution and accumulation of SPIONs in organs were simulated taking into consideration their penetration through capillary walls and their active uptake by specialized macrophages in the liver, spleen and lungs. To estimate the kinetics of SPION uptake, a novel experimental approach using primary macrophages was developed. The murine PBPK model was validated against in vivo pharmacokinetic data, and accurately described accumulation in liver, spleen and lungs. After validation of the murine model, a similar PBPK approach was developed to simulate the distribution of SPIONs in humans. These data demonstrate the utility of PBPK modeling for estimating biodistribution of inorganic nanoparticles and represents an initial platform to provide computational prediction of nanoparticle pharmacokinetics.