Very small polydopamine (PDA) polyethylene glycol (PEG) crosslinked copolymer (PDA-PEG) nanoparticles have been prepared following a convenient one-step procedure in aqueous solution. Particle sizes and colloidal stabilities have been optimized by varying PEG in view of chain length and end group functionalities. In particular, amine-terminated PEG3000 [PEG3000(NH2)2] reacted with polydopamine intermediates so that very small, crosslinked PDA-PEG nanoparticles with sizes of less than 50 nm were formed. These nanoparticles remained stable in buffer solution and no sedimentation occurred. Chemical functionalization was straight-forward as demonstrated by the attachment of fluorescent dyes. The PDA-PEG nanoparticles revealed efficient cellular uptake via endocytosis and high cytocompatibility, thus rendering them attractive candidates for cell imaging or for drug delivery applications.

We demonstrate the suitability of the ToF-SIMS technique for the detection of SiO₂ nanoparticles in lung tissue sections by a comparison to fluorescence microscopy.

The description of nanoparticle distributions in tissue and associated effects is an important goal of nanotoxicology. Three-dimensional time-of-flight-secondary ion mass spectrometry (3D ToF-SIMS) is a promising label-free method to analyse tissue sections for nanoparticle distribution and to simultaneously detect organic and inorganic molecule species at high spatial resolution. As sample regions accessible to ToF-SIMS 3D imaging are limited to several hundred square micrometers, the proper selection of nanoparticle containing regions is mandatory. Micro X-ray fluorescence spectrometry (μ-XRF) provides a non-destructive, fast elemental analysis of large tissue sections with lateral resolution in the micrometer range. The latter technique was, therefore, used to screen samples as well as to validate elemental distribution images from ToF-SIMS 3D analysis. Specifically, cryo-sections from lungs inhomogeneously laden with CeO₂ nanoparticles (10–200 nm) were subjected to μ-XRF and reflected light microscopy to pre-select lung tissue areas containing CeO₂ NPs. The lateral resolution (670 nm) of ToF-SIMS imaging analyses in these areas exceeds the lateral resolution of μ-XRF imaging by a factor of 42 and reveals the lateral distribution of CeO₂ NPs within the tissue structure. In addition, simultaneously acquired further secondary ions at a mass resolution of R = 4000 shed light on the sample composition. In summary, the investigation shows that μ-XRF is highly suitable to identify relevant tissue regions for subsequent high resolution ToF-SIMS 3D microanalysis of nanoparticle-laden tissue sections.