Targeting tumor cells and neovascularization using RGD-functionalized magnetoliposomes.

Purpose: Magnetoliposomes (MLs) have shown great potential as magnetic resonance imaging contrast agents and as delivery vehicles for cancer therapy. Targeting the MLs towards the tumor cells or neovascularization could ensure delivery of drugs at the tumor site. In this study, we evaluated the potential of MLs targeting the αvβ3 integrin overexpressed on tumor neovascularization and different tumor cell types, including glioma and ovarian cancer.

Magnetoliposomes as Contrast Agents for Longitudinal in vivo Assessment of Transplanted Pancreatic Islets in a Diabetic Rat Model.

Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity.

Improved Labeling of Pancreatic Islets Using Cationic Magnetoliposomes.

Pancreatic islets (PIs) transplantation is an alternative approach for the treatment of severe forms of type 1 diabetes (T1D). To monitor the success of transplantation, it is desirable to follow the location of engrafted PIs non-invasively. In vivo magnetic resonance imaging (MRI) of transplanted PIs is a feasible cell tracking method; however, this requires labeling with a suitable contrast agent prior to transplantation.

Variability in contrast agent uptake by different but similar stem cell types.

The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters.

In vivo hepatocyte MR imaging using lactose functionalized magnetoliposomes.

The aim of this study was to assess a novel lactose functionalized magnetoliposomes (MLs) as an MR contrast agent to target hepatocytes as well as to evaluate the targeting ability of MLs for in vivo applications. In the present work, 17 nm sized iron oxide cores functionalized with anionic MLs bearing lactose moieties were used for targeting the asialoglycoprotein receptor (ASGP-r), which is highly expressed in hepatocytes. Non-functionalized anionic MLs were tested as negative controls.

Magnetically triggered clustering of biotinylated iron oxide nanoparticles in the presence of streptavidinylated enzymes.

This work deals with the production and characterization of water-compatible, iron oxide based nanoparticles covered with functional poly(ethylene glycol) (PEG)-biotin surface groups (SPIO-PEG-biotin). Synthesis of the functionalized colloids occurred by incubating the oleate coated particles used as precursor magnetic fluid with anionic liposomes containing 14 mol% of a phospholipid-PEG-biotin conjugate. The latter was prepared by coupling dimyristoylphosphatidylethanolamine (DC(14:0)PE) to activated α-biotinylamido-ω -N-hydroxy-succinimidcarbonyl-PEG (NHS-PEG-biotin).

Investigating the toxic effects of iron oxide nanoparticles.

The use of iron oxide nanoparticles (IONPs) in biomedical research is steadily increasing, leading to the rapid development of novel IONP types and an increased exposure of cultured cells to a wide variety of IONPs. Due to the large variation in incubation conditions, IONP characteristics, and cell types studied, it is still unclear whether IONPs are generally safe or should be used with caution. During the past years, several contradictory observations have been reported, which highlight the great need for a more thorough understanding of cell-IONP interactions.

How to assess cytotoxicity of (iron oxide-based) nanoparticles: a technical note using cationic magnetoliposomes.

The range of different types of nanoparticles and their biomedical applications is rapidly growing, creating a need to thoroughly examine the effects these particles have on biological entities. One of the most commonly used nanoparticle types is iron oxide nanoparticles, which can be used as MRI contrast agents. The main research topic is the in vitro labeling of cells with iron oxide nanoparticles to render the cells detectable for MRI upon in vivo transplantation.

MRI assessment of blood outgrowth endothelial cell homing using cationic magnetoliposomes.

The use of contrast material to stimulate magnetic resonance imaging (MRI) of migrating cells has become an important area of research. In the present study, cationic magnetoliposomes (MLs) were used to magnetically label human blood outgrowth endothelial cells (BOECs) and follow their homing by magnetic resonance imaging (MRI). The biodistribution and functional integration capacity of BOECs, which have shown extensive promise as gene delivery vehicles, have thus far only rarely been investigated.

Magnetoliposomes as magnetic resonance imaging contrast agents.

Among the wide variety in iron oxide nanoparticles which are routinely used as magnetic resonance imaging (MRI) contrast agents, magnetoliposomes (MLs) take up a special place. In the present work, the two main types (large and small MLs) are defined and their specific features are commented. For both types of MLs, the flexibility of the lipid coating allows for efficient functionalization, enabling bimodal imaging (e.

The labeling of cationic iron oxide nanoparticle-resistant hepatocellular carcinoma cells using targeted magnetoliposomes.

The in vitro labeling of cultured cells with nanomaterials is a frequent practice but the efficiency, specificity and cytotoxicity of labeling specific cell types using targeted nanoparticles has only rarely been investigated. In the present work, functionalized anionic lipid-coated iron oxide cores (magnetoliposomes (MLs)) bearing galactose moieties were used for the specific labeling of asialoglycoprotein receptor 1 (ASGPR-1)-expressing HepG2 cells. The optimal number of galactose moieties per particle (± 26) was determined and uptake efficiency was compared with galactose-lacking anionic and cationic MLs.

Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects.

The in vitro labeling of stem or therapeutic cells with engineered nanoparticles with the aim of transplanting these cells into live animals and, for example, noninvasively monitoring their migration, is a hot topic in nanomedicine research. It is of crucial importance that cell-nanoparticle interactions are studied in depth in order to exclude any negative effects of the cell labeling procedure. To date, many disparate results can be found in the literature regarding nanoparticle toxicity due to the great versatility of different parameters investigated.

Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling.

The in vitro labelling of cultured cells with iron oxide nanoparticles (NPs) is a frequent practice in biomedical research. To date, the potential cytotoxicity of these particles remains an issue of debate. In the present study, 4 different NP types (dextran-coated Endorem, carboxydextran-coated Resovist, lipid-coated magnetoliposomes (MLs) and citrate-coated very small iron oxide particles (VSOP)) are tested on a variety of cell types, being C17.

Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality.

Iron oxide nanoparticles (NPs) are frequently employed in biomedical research as magnetic resonance (MR) contrast agents where high intracellular levels are required to clearly depict signal alterations. To date, the toxicity and applicability of these particles have not been completely unraveled. Here, we show that endosomal localization of different iron oxide particles results in their degradation and in reduced MR contrast, the rate of which is governed mainly by the stability of the coating.

Background migration of USPIO/MLs is a major drawback for in situ labeling of endogenous neural progenitor cells.

MR-labeling of endogenous neural progenitor cells (NPCs) to follow up cellular migration with in vivo magnetic resonance imaging (MRI) is a very promising tool in the rapidly growing field of cellular imaging. To date, most of the in situ labeling work has been performed using micron-sized iron oxide particles. In this work magnetoliposomes (MLs), i.

PEGylated lipids impede the lateral diffusion of adsorbed proteins at the surface of (magneto)liposomes.

Protein binding to nanoparticles is a crucial issue in biomedicine, as it triggers their clearance from the bloodstream after intravenous injection. Many techniques are available for measuring strong protein binding interactions, but weak dynamic interactions are more difficult to assess. To tackle the latter problem, in the present work, cytochrome c was chosen as a representative model of a water-soluble protein and the adsorbing particulates were either small unilamellar phospholipid vesicles or 14 nm diameter solid superparamagnetic iron oxide cores onto which a phospholipid bilayer was strongly chemisorbed (so-called magnetoliposomes).

Evaluation of peri-tumoral vessels surrounding colorectal liver metastases after intravenous injection of extruded magnetoliposomes in rats: correlation with 3T MRI and histopathology.

Background: Magnetoliposomes have pronounced signal-enhancing effect on T1-weighted (T1w) images of the liver using qualitative analysis which may be benefical for demonstrating peritumoral vasculature.

Purpose: To correlate peri-tumoral vasculature (ring-enhancement) surrounding colorectal liver metastases after injection of magnetoliposomes using T1-weighted (T1w) imaging with histopathology in a rat model.

Material And Methods: All experiments were approved by the responsible Animal Care Committee.

High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling.

Iron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported.

Biodistribution and pharmacokinetics of PEG-10kDa-cholecystokinin-10 in rats after different routes of administration.

Cholecystokinin, produced in the proximal small intestine, is a short acting satiating peptide hormone. CCK-10, before and after mono-iodination, was previously coupled to 10kDa polyethylene glycol (PEG). The formed conjugates PEG10kDa-CCK-10 and PEG10kDa-[(127)I]-CCK-10 show after i.

Cationic magnetoliposomes.

Magnetoliposomes (MLs) consist of nanosized, magnetisable iron oxide cores (magnetite, Fe(3)O(4)) which are individually enveloped by a bilayer of phospholipid molecules. To generate these structures, the so-called water-compatible magnetic fluid is first synthesized by co-precipitation of Fe(2+) and Fe(3+) salts with ammonia and the resulting cores are subsequently stabilized with lauric acid molecules. Incubation and dialysis of this suspension with an excess of sonicated, small unilamellar vesicles, ultimately, results in phospholipid-Fe(3)O(4) complexes which can be readily captured from the solution by high-gradient magnetophoresis (HGM), reaching very high yields.

Assessing cytotoxicity of (iron oxide-based) nanoparticles: an overview of different methods exemplified with cationic magnetoliposomes.

Iron oxide nanoparticles are the most widely used T(2)/T(2)* contrast agents and for biomedical research purposes, one of the main applications is the in vitro labeling of stem or therapeutic cells, allowing them to be subsequently tracked in vivo upon transplantation. To allow this, the nanoparticles used should not show any sign of cytotoxicity and not affect cellular physiology as this could impede normal cell functionality in vivo or lead to undesired side-effects. Assessing the biocompatibility of the nanoparticles has proven to be quite a difficult task.

The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes.

Magnetoliposomes (MLs), built up of ultrasmall iron oxide cores each individually surrounded by a lipid bilayer, have emerged as highly biocompatible nanoparticles and promising tools in many biomedical applications. To improve cell uptake, cationic amphiphiles are inserted into the ML coat, but this often induces cytotoxic effects. In the present work, we synthesized and tested a cationic peptide-lipid conjugate (dipalmitoylphosphatidylethanolamine-succinyl-tetralysine [DPPE-succ-(Lys)4]) which is entirely composed of biodegradable moieties and specifically designed to exert minimal cytotoxic effects.

Addressing the problem of cationic lipid-mediated toxicity: the magnetoliposome model.

The high biocompatibility and versatile nature of liposomes made these particles keystone components in many hot-topic research areas. For transfection and cell labelling purposes, synthetic cationic lipids are often added, but in most studies, little attention has been paid to their cytotoxic effects. In the present work, cationic magnetoliposomes (MLs), i.

Magnetoliposomes: versatile innovative nanocolloids for use in biotechnology and biomedicine.

The high biocompatibility and versatile nature of liposomes have made these particles keystone components in many hot-topic biomedical research areas. Liposomes can be combined with a large variety of nanomaterials, such as superparamagnetic iron oxide nanocores. Because the unique features of both the magnetizable colloid and the versatile lipid bilayer can be joined, the resulting so-called magnetoliposomes can be exploited in a great array of biotechnological and biomedical applications.

Stable long-term intracellular labelling with fluorescently tagged cationic magnetoliposomes.

Iron oxide nanocrystals that are dextran coated are widely exploited biomedically for magnetic resonance imaging (MRI), hyperthermia cancer treatment and drug or gene delivery. In this study, the use of an alternative coating consisting of a phospholipid bilayer directly attached to the magnetite core is described. The flexible nature of the magnetoliposome (ML) coat, together with the simple production procedure, allows rapid and easy modification of the coating, offering many exciting possibilities for the use of these particles in biomedical applications.