Protein Corona Attenuates the Targeting of Antitumor Sialyl Lewis X-Decorated Liposomes to Vascular Endothelial Cells under Flow Conditions

Abstract

Previously, we showed in the human umbilical vein endothelial cells (HUVECs) model that a liposome formulation of melphalan lipophilic prodrug (MlphDG) decorated with selectin ligand tetrasaccharide Sialyl Lewis X (SiaLeX) undergoes specific uptake by activated cells and in an in vivo tumor model causes a severe antivascular effect. Here, we cultured HUVECs in a microfluidic chip and then applied the liposome formulations to study their interactions with the cells in situ under hydrodynamic conditions close to capillary blood flow using confocal fluorescent microscopy. The incorporation of 5 to 10% SiaLeX conjugate in the bilayer of MlphDG liposomes increased their consumption exclusively by activated endotheliocytes. The increase of serum concentration from 20 to 100% in the flow resulted in lower liposome uptake by the cells. To elucidate the possible roles of plasma proteins in the liposome–cell interactions, liposome protein coronas were isolated and analyzed by shotgun proteomics and immunoblotting of selected proteins. Proteomic analysis showed that a gradual increase in SiaLeX content correlated with the overall enrichment of the liposome-associated proteins with several apolipoproteins, including the most positively charged one, ApoC1, and serum amyloid A4, associated with inflammation, on the one hand, and a decrease in the content of bound immunoglobulins, on the other. The article discusses the potential interference of the proteins in the binding of liposomes to selectins of endothelial cells.

Organic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis

“…While more technological advancements are required before non-invasive imaging technologies like conventional ultrasound, CT, and MR can be widely used, they may provide lower-risk alternatives for characterizing atherosclerotic plaque. Using contrast agents, or tracers, has been one of the advances in MR angiography as it can decrease scan time, reduce artifacts, and improve image clarity [72,73]. Nanoparticles can decrease the toxicity of tracers and carry surfacetargeting ligands to improve residence time and target cell/tissue delivery specificity, much like they can increase the efficiency of drug and gene delivery.…”

Editorial for Special Issue: “Liposomal and Lipid-Based Drug Delivery Systems and Vaccines”

“…The original research papers published in this Special Issue present new perspectives of the development of liposomal small-molecule drugs designed for different indications and modes of administration [ 1 , 2 , 3 ], anti-cancer immunogenic liposomes [ 4 ], lipid-based formulations with siRNA [ 5 ], and mRNA for effective transfection in vitro [ 6 , 7 ] and in vivo [ 8 ]. One review [ 9 ] considers the rational design of liposomal gene delivery systems that target the folic acid receptor.…”

“…Gamaleya Research Institute, and V.N. Orekhovich Institute of Biomedical Chemistry—demonstrates the effect of the protein corona of targeted antitumor liposomes on internalization by human endothelial cells under the conditions of modeling microvessels in a microfluidic device [ 3 ]. The ability of fluid-phase liposomes, loaded with the lipophilic prodrug of melphalan and decorated with a tetrasaccharide selectin ligand SiaLe X , to target activated endotheliocytes was maintained under microflow conditions.…”