Abstract
Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments.
Highlights
Delivery of therapeutic agents in specific brain areas is a major challenge for the treatment of most neurological disorders
On the basis of these considerations, this work aimed at evaluate in vitro, in primary cultures of rat astrocytes, the toxicity of polyethylene glycol (PEG)-terminated phospholipid micelles embedding luminescent NCs, namely core shell nanostructures consisting of a cadmium sulphide core and a zinc sulphide shell (CdSe@ZnS)
In order to investigate the effect of end groups and charge at the micelle surface, cytotoxicity studies were performed on empty PEG-lipid micelles formed of bare PEG-2-PE and of a mixture of PEG-2-PE and DSPE-PEG-NH2 or DSPE-PEG-COOH, respectively
Summary
Delivery of therapeutic agents in specific brain areas is a major challenge for the treatment of most neurological disorders. Many activities potentially able to revolutionize diagnosis and treatment of neurological diseases, have been developed in the field of nanomaterials [4,5]. In this perspective, neuroscience specific applications of emitting semiconductor colloidal nanocrystals (NCs) have been demonstrated relevant in cellular imaging and medical diagnosis of neurological disorders [6,7,8]. Despite the growing literature on the use of luminescent NCs as imaging and diagnosis agents on a wide variety of cell types, typically tumor cells or immortalized cells, only a limited number of studies have so far explored their applications in primary neurons, glia and related cells [10,12]. While a proper functionalization of NC surface is essential in order to limit the toxicity, preliminary studies assessing the toxicity of the resulting nanostructure in vitro in cell culture systems before their use for clinical purposes in any animal subject is fundamental
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