Integrin Targeting and Toxicological Assessment of Peptide‐Conjugated Liposome Delivery Systems to Activated Endothelial Cells

Abstract

Utilization of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide‐conjugated cationic liposomes were constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide‐conjugated liposomes induced only cytotoxicity at the highest concentration in non‐activated or activated endothelial cells, as well as in co‐culture of endothelial cells and macrophages. There was unaltered secretion of cytokines after exposure of peptide‐conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated endothelial cells, as compared to a liposome with a peptide that targeted both the fibronectin and vitronectin receptors, as well as liposomes with a control peptide. The liposome targeted to the fibronectin receptor also displayed uptake in endothelial cells in co‐culture with activated macrophages. Therefore, this study demonstrates the feasibility of constructing a peptide‐conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells.

A Flow Cytometry‐based Method for the Screening of Nanomaterial‐induced Reactive Oxygen Species Production in Leukocytes Subpopulations in Whole Blood

“…Hence, one would expect preferential interaction of NMs with these specific cell populations. As a side note, it should be stated that the liposome-related data in this study fit very well with a previous investigation in which a comprehensive in vitro analysis found that potential adverse effects after exposure of endothelial cells and macrophages to liposomes did not induce a cytotoxic or inflammatory response in any of the experimental conditions [36]. In addition, the same liposomes were also shown to be highly biocompatible after intravenous exposure of C57BL/6 mice [42].…”

“…As a side note, the liposomes were shown to be stable for at least three months after the initial extrusion [36]. The measurements of NM size were not carried out in whole blood as the protein content in serum makes these assessments impossible.…”

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

“…NPs containing ligands for these receptors demonstrate significantly higher selectivity and transfection efficiency 54–56 . The mannose receptor (MR), which is a C‐type lectin I transmembrane protein, is believed to be a promising target for nanocarriers 57 . The MR is expressed on dendritic cells, tissue macrophages, and liver sinusoidal endothelial cell 58 .…”

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

“…For example, NP surfaces can be chemically designed to influence site-specific drug delivery, as well as the kinetics of drug release. 9,12 In addition to drug delivery, the discovery of quantum effects (size-dependent properties) that result in materials with specific emission, absorption, or light-scattering spectra has expanded potential applications in imaging and diagnosis. 11 Further advantages of the use of NPs can include improved drug stability and longer shelf-life 9 compared with traditional formulations.…”

“…21 Once in the submucosal tissue, NPs can enter the lymphatics and the blood capillaries. 12 The remainder of the manuscript examines the progress made in utilization of nanoscale carriers or stabilized soliddrug NPs in medical applications following oral route of administration. The search criteria included a combination of the following terms: "nanomedicine", "nanoparticles", "nanomaterials", "in vivo", "liposomes", "micelles", "solid drug nanoparticles", "oral route", "oral exposure", "oral administration", "gastrointestinal tract", "nanodelivery" "nanocarrier", "nanovehicles", "nanoconstructs", "nanoemulsions", "adverse effects", "toxicity", "cytotoxicity", "drug delivery", "therapeutics", "imaging", "systemic", and "Caco-2 cells".…”