Abstract
Lipid structures, such as liposomes or micelles, are of high interest as an approach to support the transport and delivery of active agents as a drug delivery system. However, there are many open questions regarding their uptake and impact on cellular metabolism. In this study, lipid structures were assembled as a supported lipid bilayer on top of biopolymer-coated microcarriers based on the Layer-by-Layer assembly strategy. The functionalized microcarriers were then applied to various human and animal cell lines in addition to primary human macrophages (MΦ). Here, their influence on cellular metabolism and their intracellular localization were detected by extracellular flux analysis and immunofluorescence analysis, respectively. The impact of microcarriers on metabolic parameters was in most cell types rather low. However, lipid bilayer-supported microcarriers induced a decrease in oxygen consumption rate (OCR, indicative for mitochondrial respiration) and extracellular acidification rate (ECAR, indicative for glycolysis) in Vero cells. Additionally, in Vero cells lipid bilayer microcarriers showed a more pronounced association with microtubule filaments than polymer-coated microcarrier. Furthermore, they localized to a perinuclear region and induced nuclei with some deformations at a higher rate than unfunctionalized carriers. This association was reduced through the application of the microtubule polymerization inhibitor nocodazole. Thus, the effect of respective lipid structures as a drug delivery system on cells has to be considered in the context of the respective target cell, but in general can be regarded as rather low.
Highlights
The research topic of smart nanocarriers has gained much attention since their successful application as a delivery system for mRNA vaccines, including the SARS-CoV-2 spike protein [1,2]
Extracellular flux analysis was used for assessment of mitochondrial respiration and glycolysis through simultaneous measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), respectively
Metabolic properties of a given cell type and the reliance on a more aerobic or anaerobic phenotype were addressed by the OCR/ECAR ratio calculated from basal OCR
Summary
The research topic of smart nanocarriers has gained much attention since their successful application as a delivery system for mRNA vaccines, including the SARS-CoV-2 spike protein [1,2] Their application in cancer immunotherapeutics for the transport of immune modulators is of high interest as the activation of a humoral or cellular immune response could support recognition and eventually killing of tumour cells, and as such the elimination of the entire tumour [3,4,5]. In this context, artificial lipids as part of functionalized liposomes and micelles or as a supported bilayer on top of other drug delivery systems are of special interest. An alteration in the metabolic state of the target cell would point toward a modulation of cellular functions by the carrier and potential off-target effects that could occur besides effects by the delivered compound
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