Abstract

There is considerable interest in developing diagnostic nanotools for early detection and delivery of  various therapeutic agents for treatment of neurodegenerative diseases. However, a key challenge  remains in the selection of suitable surfaces to overcome the nano–bio interface issue, namely that many  nanoparticle surfaces demonstrate instability when administered into biological environments and show  substantial cytotoxicity to the central nervous system. In this study, we fabricated an evaluation platform  for bio–nano surface selection based on the combination of upconversion nanoparticles (UCNPs),  cultured neural cells and zebra fish, and systemically demonstrated how it can evaluate the suitability of  nanoparticle surfaces for applications in the central nervous system. Firstly, we fabricated highly lanthanidedoped  UCNPs, which generate the strongest tissue penetrable emission at 800 nm. We then functionalized  these UCNPs with four popular surfaces for evaluation. Next, we systematically evaluated the spectral emission  properties, biophysical stability, cytotoxicity and cell uptake capability of these surface-functionalized  UCNPs in biological solutions or with cultured NSC-34 cells. Through these studies, PEG-COOH proved to  be the superior surface modification. Accordingly, we further confirmed the bioavailability of unmodified  and surface modified UCNPs in the spinal cord of living zebrafish. As predicted, PEG-UCNPs displayed  excellent dispersal and uptake into spinal motor neurons in living zebrafish. Collectively, this study developed  a versatile upconversion platform for systematic evaluation of nanoparticle surfaces, which can  provide valuable information via systemic surface evaluation in vitro and in vivo for future construction of  multifunctional nanosystems for theranostic applications in neurodegenerative diseases.