RESUMEN
Magnetic nanoparticles can be functionalized in many ways for biomedical applications. Here, we combine four advantageous features in a novel Fe-Pt-Yb2O3 core-shell nanoparticle. (a) The nanoparticles have a size of 10 nm allowing them to diffuse through neuronal tissue. (b) The particles are superparamagnetic after synthesis and ferromagnetic after annealing, enabling directional control by magnetic fields, enhance NMRI contrast, and hyperthermia treatment. (c) After neutron-activation of the shell, they carry low-energetic, short half-life ß-radiation from 175Yb, 177Yb, and 177Lu. (d) Additionally, the particles can be optically visualized by plasmonic excitation and luminescence. To demonstrate the potential of the particles for cancer treatment, we exposed cultured human glioblastoma cells (LN-18) to non-activated and activated particles to confirm that the particles are internalized, and that the ß-radiation of the radioisotopes incorporated in the neutron-activated shell of the nanoparticles kills more than 98% of the LN-18 cancer cells, promising for future anti-cancer applications.
RESUMEN
The pH is one of the key parameters governing protein conformation and activity. In protein crystals, however, the pH is so far not accessible by experiment. Here, we report on the optical detection of the pH in a lysozyme crystal employing the pH-sensitive fluorescent dyes SNARF-1 and SNARF-4F. The molecular probes were loaded into the crystal by diffusion. Two-dimensional fluorescence spectra of the labeled protein crystal were recorded, and the average pH of the crystal at different bath pH's was determined by calibrating fluorescence peak ratios. In addition, we used two-photon microscopy to spatially resolve the pH inside a lysozyme crystal three-dimensionally and to follow pH changes in response to a pH change of the bath over time. At equilibrium at bath pH between 5.5 and 8.0, we found a pH in the water-filled crystal channels that was ΔpH = -0.3 to -1.0 lower than that of the bath. This corresponds to a 2- to 10-fold higher proton concentration in the crystal channels than in the bath. The lower pH at equilibrium in the crystal channels can be explained by slower proton diffusion in the channels than in the bath and a resulting proton accumulation in the crystal for conservation of mass and so an equilibrium of proton flux.