Search Results
Estimating the modulatory effects of nanoparticles on neuronal circuits using computational upscaling
2013, Busse, Michael, Stevens, David, Kraegeloh, Annette, Cavelius, Christian, Vukelic, Mathias, Arzt, Eduard, Strauss, Daniel J.
Background: Beside the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug delivery schemes are already in clinical trials. However the influence of the nanoparticles themselves is still unknown in medical applications, especially for complex interactions in neural systems. The aim of this study was to investigate in vitro effects of coated silver nanoparticles (cAgNP) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects on neuronal circuits. Methods: We first performed patch clamp measurements to investigate the effects of nanosized silver particles, surrounded by an organic coating, on excitability of single cells. We then determined which parameters were altered by exposure to those nanoparticles using the Hodgkin–Huxley model of the sodium current. As a third step, we integrated those findings into a well-defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAgNP, in silico. Results: We observed rapid suppression of sodium currents after exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium currents we identified the parameters likely affected by cAgNP. We then examined the effects of such changes on the activity of networks. In silico network modeling indicated effects of local cAgNP application on firing patterns in all neurons in the circuit. Conclusion: Our sodium current simulation shows that suppression of sodium currents by cAgNP results primarily by a reduction in the amplitude of the current. The network simulation shows that locally cAgNP-induced changes result in changes in network activity in the entire network, indicating that local application of cAgNP may influence the activity throughout the network.
Nanocarriers in photodynamic therapy—in vitro and in vivo studies
2019, Sztandera, Krzysztof, Gorzkiewicz, Michał, Klajnert‐Maculewicz, Barbara
Photodynamic therapy (PDT) is a minimally invasive technique which has proven to be successful in the treatment of several types of tumors. This relatively simple method exploits three inseparable elements: phototoxic compound (photosensitizer [PS]), light source, and oxygen. Upon irradiation by light with specified wavelength, PS generates reactive oxygen species, which starts the cascade of reactions leading to cell death. The positive therapeutic outcome of PDT may be limited due to several aspects, including low water solubility of PSs, hampering their effective administration and blood circulation, as well as low tumor specificity, inefficient cellular uptake and activation energies requiring prolonged illumination times. One of the promising approaches to overcome these obstacles involves the use of carrier systems modulating pharmacokinetics and pharmacodynamics of the PSs. In the present review, we summarized current in vitro and in vivo studies regarding the use of nanoparticles as potential delivery devices for PSs to enhance their cellular uptake and cytotoxic properties, and thus—the therapeutic outcome of PDT.