Lipid surface modifications increase mesoporous silica nanoparticle labeling properties in mesenchymal stem cells

Abstract

BackgroundNanoparticles have emerged as promising cell-labeling tools, as they can be precisely tailored in terms of chemical and physical properties. Mesoporous silica nanoparticles (MSNs), in particular, are easily tunable with regard to surface and core chemistry, and are able to confine dyes and drug molecules efficiently.PurposeThe aim of this study was to investigate the effect of lipid and polyethylene glycol (PEG) surface modifications on MSN stem-cell-tracking abilities.MethodsLipid and PEG surface functionalized MSNs were synthesized and the effect of surface functionalization on cell internalization, proliferation, differentiation and cell proteomics was investigated in patient derived mesenchymal stem cells (MSCs).ResultsMSNs and lipid surface-modified MSNs were internalized by >80% of the MSC population, with the exception of nanoparticles modified with short PEG chains (molecular weight 750 [MSN-PEG750]). Lipid-modified MSNs had higher labeling efficiency with maximum uptake after 2 hours of exposure and were in addition internalized 17 times higher compared to unmodified MSNs, without negatively affecting differentiation capacity. Using a mass-spectrometry-based label-free quantitative proteomics approach, we show that MSN labeling leads to the up- and downregulation of proteins that were unique for the different surface-modified MSNs. In addition, functional enrichments were found in human MSCs labeled with MSNs, MSN-PEG750, and lipid-modified MSNs.SummaryHere we show that organic modifications with lipids and PEGylation can be used as a promising strategy to improve MSN labeling capabilities. In particular, we show that lipid modifications can optimize such probes in three distinct ways: significantly improved signal strength, a barrier for sustained release of additional probes, and improved stem-cell-labeling efficiency.

Guiding mesenchymal stem cell differentiation using mesoporous silica nanoparticle-based films

“…3A and S2, right) in hMSCs cultured on the MSN films compared to those exposed to the colloidal calcein loaded MSN suspension. The uptake of calcein by hMSCs when adding MSNs in suspension was stable over 2 d, consistent with previous findings that MSNs in suspensions are internalized in hMSCs within the first few hours of culture [31].…”

“…Since the in vitro differentiation of hMSCs towards an adult lineage relies on continuous presence of bioactive molecules, we pursued the possibility of using lipid bilayer surface functionalization to slow down cargo release. The lipid surface modification has been used by us and others to create biocompatible MSNs that allow sustained cargo release by blocking the MSN pores [23,26,31]. Indeed, we could show that using a lipid bilayer, calcein delivery was significantly slowed down; both from the films and when hMSCs were cultured on MSN-DOPC films.…”

Inhibition of Extracellular Cathepsin D Reduces Hepatic Lipid Accumulation and Leads to Mild Changes in Inflammationin NASH Mice

“…For proteomics experiments, liver homogenates were used (n=3 for each group of mice). The samples were prepared as described previously (26). Briefly, proteins were extracted, reduced with 20 mM dithiothreitol for 45 minutes and alkylated with 40 mM iodoacetamide for 45 minutes in the dark.…”

“…The search engine Sequest was used with the Swiss-Prot mouse database (Mus musculus, TaxID 10090). The settings for the database search were similar as before (26). Proteins with a falsediscovery rate ≤ 1% were considered for the analysis and were normalized to the total peptide amount.…”

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

“…The in vivo tracking of transplanted stem cells allows a guided and more precise therapy. Rosenbrand et al showed that modifications of MSNs with lipids and PEG can improve their ability for stem-cell tracking by increasing the labeling efficiency and signal intensity [ 319 ]. Kempen et al synthesized MSNs to serve as both drug carriers and labeling agents for ultrasound and MRI [ 320 ].…”