Abstract
The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0128-y) contains supplementary material, which is available to authorized users.
Highlights
Dendritic polymers feature versatile molecular architectures with multifunctional properties [1,2,3,4,5,6]
The observed toxic effects of the nanoparticles seem to be on the one hand dependent on the used concentrations and on the other hand on the molecular weight of the poly(ethylene imines) (PEI) core
In summary we have demonstrated that maltose-modified poly(ethylene imine) (PEI)nanoparticles with PEI-5k and PEI-25k core feature a good uptake in primary mesenchymal stem cells
Summary
Dendritic polymers feature versatile molecular architectures with multifunctional properties [1,2,3,4,5,6]. Tailored by the fabrication of the dendritic scaffold, the resulting dendritic polymers can provide multifunctional key features such as high water-solubility [7], complexing. First trials have been undertaken with dendritic polyamine scaffolds based on various (hyper-) branched poly(ethylene imines) (PEI) to use them as nonviral vectors for small-interfering-(si)-RNA [8, 17] and DNA [17,18,19,20]. PEI nanoparticles show on the one hand high cellular uptake rates and high transfection efficacies. For example polyglutaminic acid-chains [25], oligosaccharide units [26, 27] or different other modifications [28, 29] have been introduced to better shield the PEI-core from the biological environment
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