Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents

Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T₁-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T₁-weighted MRI/computed X-ray tomography (CT) and T₁-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality.     

Facile synthesis of ultra-small hollow manganese silicate nanoparticles as pH/GSH-responsive T1-MRI contrast agents

Manganese silicate nanoparticles have recently attracted great attention due to the effectiveness of T₁-weighted magnetic resonance imaging (MRI) contrast agents (CAs) in the mildly acidic and high glutathione (GSH) conditions of the tumor microenvironment. Herein, ultra-small hollow manganese silicate (UHMS) nanoparticles were prepared via a facile, economical, and eco-friendly method based on a hydrothermal process using small silica nanoparticles as both the silicon source and templates. The nanoparticles showed remarkable biocompatibility and dispersion stability after modification with polyethylene glycol (PEG). Owing to their ultra-high longitudinal relaxation rate (r₁) at low pH values and high GSH levels, the UHMS@PEG nanoparticles have performed an excellent pH/GSH-responsive T₁-weighted MRI. Meanwhile, the nanoparticles showed insignificant cytotoxicity in vitro and in vivo. Therefore, the UHMS@PEG nanoparticles show promise as T₁-MRI CAs in the tumor microenvironment and may be used to assist in clinical cancer diagnosis.     

Biocompatible Prussian blue nanoparticles: Preparation,stability, cytotoxicity,and potential use as an MRI contrast agent

A simple synthetic procedure for preparing biocompatible superparamagnetic Prussian blue (PB) nanoparticles is reported. The stability, cytotoxicity and ability for PB nanoparticles to penetrate cells are investigated. The potential of using PB nanoparticles as the T₁-weighted MRI contrast agent is demonstrated.     

Carbon-coated iron oxide nanoparticles as contrast agents in magnetic resonance imaging

Coprecipitated ferrite nanoparticles were coated with carbon using a hydrothermal method. From transmission electron microscope pictures, we could see that the coated iron oxide nanoparticles were spherical in shape with an average diameter of 90 nm. The strong bonding of carbon on the nanoparticle surfaces was checked by noting the C = O and C = C vibrations in Fourier transform infrared spectra. The spin-lattice relaxation process [T ₁] and spin-spin relaxation process [T ₂] relaxivities of hydrogen protons in the aqueous solution of coated nanoparticles were determined to be 1.139 (mM·s)^-1 and 1.115 (mM·s)^-1, respectively. These results showed that the carbon-coated iron oxide nanoparticles are applicable as both T ₁ and T ₂ contrast agents in magnetic resonance imaging.     

Development of biocompatible NaGdF4: Er3+, Yb3+ upconversion nanoparticles used as contrast agents for bio‐imaging

Upconversion nanoparticles with special fluorescence and magnetic properties have been considered an alternative contrast agent for multiple bio‐imaging techniques. It is important to understand the effects of the surface properties and dosage of upconversion nanoparticles on both the magnetic resonance (MRI) image and the photoluminescence spectrum. Here, NaGdF₄: Er³⁺, Yb³⁺ upconversion nanoparticles (UCNPs) modified with amine functional group were produced through a one‐pot thermal decomposition. The average length of the cubic UCNPs is estimated at 53 ±13 nm. The effect of the dosage of amine modified UCNPs on the MRI image is investigated. The T₁ and T₂ relaxivities of the amine modified UCNPs in agarose gel at 3 T are r₁ = 6.79 ±0.14 and r₂ = 17.0 ±0.18 (mmol/L)^?1 s^?1, which are comparable to the relaxivities of commercially available MRI contrast agents. In addition, the photoluminescence of the amine modified UCNPs at low concentrations < 150 µg/mL are further investigated with the excitation wavelength (λ_ex) at 980 nm. The internalization of the amine modified UCNPs cultured with human umbilical vascular endothelial cells (HUVEC) is observed by the fluorescence imaging. Meanwhile, T₁‐weighted MRI imaging of HUVEC cells treated with amine modified UCNPs at 10 µg/mL can be obtained. No significant toxic effect on cells is found when the concentration of the amine modified UCNPs is < 300 µg/mL. This study indicates that a low concentration of amine‐modified NaGdF₄: Er³⁺, Yb³⁺ UCNPs can be used as the contrast agent for both fluorescence imaging and magnetic resonance imaging.     

Enhancement of fluorescence and magnetic properties of CeF3:RE3+ (Tb,Gd) nanoparticles via multi-band UV excitation and Li doping regulation

In this study, hydrothermal synthesis of CeF₃: Tb, Gd nanoparticles doped with Li⁺ alkali metal ions were demonstrated using introduction of Li⁺ ions through LiNO₃ nitrate. These nanoparticles have dual properties of magnetic fluorescence. X-ray diffraction, Fourier transform infrared spectrometer, XPS and photoluminescence spectra, and vibrating sample magnetometry were used to characterize structural properties, surface functional groups, fluorescence, and magnetic properties of these particles. Results show that CeF₃: Tb, Gd nanoparticles exhibit bright green light emission under excitation at 258 nm and 378 nm ultraviolet band. Through the modification of Li⁺ ions, luminous intensity of green light is further improved. Energy transfer between rare earth ions was investigated via photoluminescence spectroscopy. This work demonstrates potential applications of Li doped CeF₃: Tb, Gd nanoparticles as photomagnetic dual-functional materials in fields of biological imaging, solid state lighting, and magnetic biological separation.     

Gadolinium‐conjugated FA‐PEG‐PAMAM‐COOH nanoparticles as potential tumor‐targeted circulation‐prolonged macromolecular MRI contrast agents

The aim of research is to develop potential tumor‐targeted circulation‐prolonged macromolecular magnetic resonance imaging (MRI) contrast agents without the use of low molecular gadolinium (Gd) ligands. The contrast agents were based on polymer–metal complex nanoparticles with controllable particle size to achieve the active and passive tumor‐targeted potential. In particular, poly (amidoamine) (PAMAM) dendrimer with 32 carboxylic groups was modified with folate‐conjugated poly (ethyleneglycol) amine (FA‐PEG‐NH₂, M_w: 2 k and 4 kDa). FA‐PEG‐PAMAM‐Gd macromolecular MRI contrast agents were prepared by the complex reaction between the carboxylic groups in PAMAM and GdCl₃. The structure of FA‐PEG‐PAMAM‐COOH was confirmed by nuclear magnetic resonance (¹H‐NMR), Fourier transform infrared (FTIR) spectra, and electrospray ionization mass spectra (ESI‐MS). The mass percentage content of Gd (III) in FA‐PEG‐PAMAM‐Gd was measured by inductively coupled plasma‐atomic emission spectrometer (ICP‐AES). The sizes of these nanoparticles were about 70 nm measured by transmission electron microscopy, suggestion of their passive targeting potential to tumor tissue. In comparison with clinically available small molecular Gadopentetate dimeglumine, FA‐PEG‐PAMAM‐Gd showed comparable cytotoxicity and higher relaxation rate, suggestion of their great potential as tumor‐targeted nanosized macromolecular MRI contrast agents due to the overexpressed FA receptor in human tumor cell surfaces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd₂O₃-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner.As a result, the nanoparticle sizes of Gd₂O₃-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal (r₁) and transverse relaxivity (r₂) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r₂/r₁ ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd₂O₃-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively.The achievement of new synthesis route of Gd₂O₃-DEG resulted in lower r₂/r₁ ratio for Gd₂O₃-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r₂/r₁ ratios of two PEGylated-SPGO contrast agents in our study in comparison with r₂/r₁ ratio of previous PEGylation (r₂/r₁ = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.     

Development of intravascular contrast agents for MRI using gadolinium chelates

Two MRI contrast agents (CAs) composed of Gd‐DO3A conjugated to amino acid building blocks derived from glutamic acid ( CA1 ) and lysine ( CA2 ) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mM . The longitudinal relaxivities (r₁) of CA1 and CA2 measured at 9.4 T are 6.4 and 5.4 mM ^?1 s^?1 in H₂O at 25 °C, respectively. Both r₁ values are higher than those of CAs in clinical use: Gd‐DTPA (Magnevist, Bayer Schering, Germany) and Gd‐DOTA (Dotarem, Guerbet, France). In vivo imaging in Wistar rats demonstrated considerable signal enhancement (～50 %) in the brain artery by CA2 , but lower signal enhancement (～30 %) by CA1 . In contrast to Dotarem, which showed a similar signal enhancement as CA2 , the enhancement by CA2 remained high (～30 %), even at 52 min post‐injection. This demonstrates that CA2 has a much longer blood half‐life (68.1 min), which could be advantageous for angiography and tissue targeting.     

Binding and Release of FeIII Complexes from Glucan Particles for the Delivery of T1 MRI Contrast Agents

Yeast-derived β-glucan particles (GPs) are a class of microcarriers under development for the delivery of drugs and imaging agents to immune-system cells for theranostic approaches. However, the encapsulation of hydrophilic imaging agents in the porous GPs is challenging. Here, we show that the unique coordination chemistry of Fe^III-based macrocyclic T₁ MRI contrast agents permits facile encapsulation in GPs. Remarkably, GPs labeled with the simple Fe^III complexes are stable under physiologically relevant conditions, despite the absence of amphiphilic groups. In contrast to the free Fe^III coordination complex, the labeled Fe^III-GPs have lowered T₁ relaxivity and act as a silenced form of the contrast agent. Addition of a fluorescent tag to the Fe^III complex produces a bimodal agent to further enable tracking of the nanoparticles and to monitor release. Treatment of the iron-labeled GPs with a maltol chelator or with mildly acidic conditions releases the intact iron complex and restores enhanced T₁ relaxation of the water protons.     

Magnetite/Polypyrrole Hybrid Nanocomposites as a Promising Magnetic Resonance Imaging Contrast Material

We have prepared magnetite nanoparticles (Fe₃O₄_NPs) almost spherical in shape with average particle size of 10 nm and successfully encapsulated them in an envelope of polypyrrole (PPY) chains via an emulsion polymerization route using sodium dodecyl sulfate as surfactant. The resulting PPY‐coated Fe₃O₄_NPs (Fe₃O₄_NPs/PPY) suspensions were stable with particles exhibiting a triangular prismatic morphology and an average diameter below 100 nm. In fact, all colloidal solutions were stable in aqueous media with typical ζ‐surface potential values of ?33.9 mV (Fe₃O₄_NPs) and ?20.0 mV (Fe₃O₄_NPs/PPY). Although X‐ray diffraction studies revealed the presence of a magnetic phase Fe₃O₄, the identified diffraction peaks are consistent with the presence of a spinel structure of magnetite. A ferromagnetic behavior, such as lower coercive force (H_c = 0.065 T), was observed for all magnetic nanoparticles examined. The ¹H NMR relaxation times T₁ and T₂ of selected Fe₃O₄_NPs/PPY samples were also measured and their relaxivities r₁ (1.1 s^?1 mM^?1) and r₂ (61.9 s^?1 mM^?1) compare favorably to those of contrast agents commercially used in human examinations. We suggest that the present results indicate that these hybrid nanocomposites are promising materials for the development of a platform of specialized contrast agents for ¹H Magnetic Resonance Imaging. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Synthesis and characterization of a new water-soluble endohedral metallofullerene for MRI contrast agents

Water-soluble amino acid derivatives of gadolinium (Gd) endohedral metallofullerenes (AAD-EMFs), Gd@C₈₂O_m(OH)_n(NHCH₂CH₂COOH)_l (m ≈ 6, n ≈ 16 and l ≈ 8) are synthesized by a direct reaction of the pure endohedral metallofullerene Gd@C₈₂ with an excess of alkaline solution of β-alanine. The structure of the AAD-EMFs is characterized by FTIR, XPS and laser-desorption time-of-flight (LD-TOF) mass spectrometries. Water proton relaxivity analysis indicates that the longitudinal relaxivity R₁ (the effect on 1/T₁, 9.1 mM⁻¹ s⁻¹) of AAD-EMFs is higher than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA, 5.6 mM⁻¹ s⁻¹). The MRI phantom studies are performed to confirm the high efficiency of this sample as MRI contrast agents.     

Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine-iron oxide for MR imaging of lymph nodes

The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)–C₁₆-iron oxide (PHEA-C₁₆-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C₁₆-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C₁₆-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution. The size of the nanoparticles was controlled by the amount of C₁₆. The 3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after intravenous administration of PHEA-C₁₆-iron oxide with the size of 20 nm. The in vitro and in vivo toxicity tests revealed the high biocompatibility of PHEA-C₁₆-iron oxide nanoparticles. Therefore, PHEA-C₁₆-iron oxide nanoparticles with 20-nm size can be potentially useful as T2-weighted MR imaging contrast agents for the detection of lymph nodes.     

Sol–gel auto combustion synthesis of CoFe2O4/1-methyl-2-pyrrolidone nanocomposite: Its magnetic characterization

A magnetic nanocomposite was generated by the sol–gel auto-combustion method in the presence of 1-methyl-2-pyrrolidone, a functional solvent. The temperature-dependent magnetic properties of the CoFe₂O₄ nanoparticles have been extensively studied in the temperature range of 10–400 K and magnetic fields up to 80 kOe. Zero field cooled (ZFC) and field cooled (FC) curves indicate that the blocking temperature (T_B) of the CoFe₂O₄ nanoparticles is above 400 K. It was found from M–H curves that the low temperature saturation magnetization values are higher than bulk value of CoFe₂O₄. The saturation magnetization (M_s), remanence magnetization (M_r), reduced remanent magnetization (M_r/M_s) and coercive field (H_c) values decrease with increasing temperature. The M_r/M_s value of 0.75 at 10 K indicates that the CoFe₂O₄ nanoparticles used in this work have, as expected, cubic magnetocrystalline anisotropy according to the Stoner–Wohlfarth model. T^1/2 dependence of the coercive field was observed in the temperature range of 10–400 K according to Kneller's law. The extrapolated T_B and the zero-temperature coercive field values calculated according to Kneller's law are almost 427 K and 13.2 kOe, respectively. The room temperature H_c value is higher than that of the previously reported room temperature bulk values. The effective magnetic anisotropy constant (K_eff) was calculated as about 0.23×10⁶ erg/cm³ which is lower than that of the bulk value obtained due to disordered surface spins.     

Synthesis and magnetic relaxation properties of new Gd(III) complexes derived from DTPA-bis(amide) conjugates of arylpiperazinyl amines

Two new Gd(III) complexes 1 and 2 of the type [Gd(L)H₂O]·nH₂O were synthesized from DTPA-bis(amide) conjugates of arylpiperazinyl amines. The relaxivity (R₁) of these complexes was measured in deionized water, which revealed that complex 2 had a higher relaxivity than 1 and Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of 1 and 2 indicated that they are non-toxic which warrant their physiological suitability as potential contrast agents for MRI. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods including elemental analysis, ¹H NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry.     

Investigating the Role of Sulfate Groups for the Binding of Gd3+ Ions to Glycosaminoglycans with NMR Relaxometry

Glycosaminoglycans (GAGs) are highly negatively charged macromolecules with a large cation binding capacity, but their interaction potential with exogeneous Gd³⁺ ions is under-investigated. These might be released from chelates used as Gadolinium-based contrast agents (GBCAs) for clinical MR imaging due to transmetallation with endogenous cations like Zn²⁺. Recent studies have quantified how an endogenous GAG sequesters released Gd³⁺ ions and impacts the thermodynamic and kinetic stability of some GBCAs. In this study, we investigate and compare the chelation ability of two important GAGs (heparin and chondroitin sulfate), as well as the homopolysaccharides dextran and dextran sulfate that are used as models for alternative macromolecular chelators. Our combined approach of MRI-based relaxometry and isothermal titration calorimetry shows that the chelation process of Gd³⁺ into GAGs is not just a long-range electrostatic interaction as proposed for the Manning model, but presumably a site-specific binding. Furthermore, our results highlight the crucial role of sulfate groups in this process and indicate that the potential of a specific GAG to engage in this mechanism increases with its degree of sulfation. The transchelation of Gd³⁺ ions from GBCAs to sulfated GAGs should thus be considered as one possible explanation for the observed long-term deposition of Gd³⁺ in vivo and related observations of long-term signal enhancements on T₁-weighted MR images.     

Augmenting the photocatalytic performance of cobalt ferrite via change in structural and optical properties with the introduction of different rare earth metal ions

In the present study, synthesis of different rare earth (RE) doped cobalt ferrite nanoparticles was done via facile sol-gel auto-combustion method using four different RE metal ions: Eu, Gd, Dy and Nd. The RE substituted cobalt ferrite nanoparticles were then characterized using FT-IR, powder XRD, HR-TEM, SAED, EDX, VSM and DRS techniques. From the characterization results, a significant variation in the structural, magnetic and optical properties of pure cobalt ferrite was observed with the introduction of different RE metal ions. This change in the properties was emerged due to the distortion of the ferrite crystal lattice due to replacement of smaller ionic radii Fe³⁺ ions with the comparatively larger ionic radii RE³⁺ metal ions. The catalytic activity of the fabricated RE doped cobalt ferrite nanoparticles was studied for the photo-Fenton degradation of cationic and anionic dyes. Under visible light irradiation, the as prepared RE doped nanoparticles exhibited great enhancement in the photo-Fenton degradation of dye molecules as compared to pure cobalt ferrite nanoparticles. The enhancement in the degradation rate was ascribed to the generation of defects in the crystal lattice, lower crystallite size and reduced band gap energy values which facilitated the facile transfer of photo-generated holes and electrons. Best catalytic results were obtained for CoNd_0.08Fe_1.92O₄ for SO dye (k?=?2.23?×?10^?1 min^?1) which were found to be around 9 times higher than the pure cobalt ferrite nanoparticles (k?=?0.23?×?10^?1 min^?1).     

Paramagnetic,NIR‐luminescent Nd3+‐ and Gd3+‐doped fluorapatite as contrast agent for multimodal biomedical imaging

Combining near infrared (NIR) luminescence and magnetic resonance (MR) contrasts in a crystal host is highly desirable for contrast agents in biomedical imaging technology, as it will enable multimodal imaging processes. In the present work, biocompatible luminescent and paramagnetic fluorapatite (FAp) nanoparticles were prepared via doping with neodymium (Nd³⁺) and gadolinium (Gd³⁺), respectively. While Nd³⁺‐doped FAp (Nd:FAp) exhibits dopant concentration‐dependent photoluminescence (PL) in the NIR spectral region, Gd³⁺‐doped FAp (Gd:FAp) shows paramagnetic behavior and strong transverse relaxation effects resulting in MR contrastive properties. Remarkably, multimodal co‐doped FAp (Nd:Gd:FAp) nanoparticles combine both properties in 1 single crystal enabling luminescence as well as MR contrast.     

Gd(III) functionalized gold nanorods for multimodal imaging applications

We demonstrate a novel noncovalent method for producing Gd(III)-functionalized gold nanorods as multimodal contrast agents for MRI and CT imaging. The ligand is connected to the surface of the gold nanorods by a noncovalent bond making the Gd(III) ions directly accessible to water molecules, and resulting in a longitudinal relaxivity as high as 21.3 mM(-1) s(-1). In addition, compared with spherical gold nanoparticles, gold nanorods have more binding sites for Gd(III) ions due to their large surface-to-volume ratio. Benefiting from the advantages of the new type of carry material and the novel fabrication approach, the multimodal imaging probes exhibit a high longitudinal relaxivity r(1) on the order of 1.1 × 10(7) mM(-1) s(-1) on a per-particle basis, which is 24 times higher than that of Gd(III)-ion-functionalized spherical gold nanoparticles. Furthermore, CT imaging shows that such nanoprobes could induce an efficient contrast enhancement when the gold concentration is at least equal to 1.31 mg ml(-1). These results demonstrate that the as-prepared Gd functionalized gold nanorods could provide a new and versatile platform for the development of multimodal imaging probes.     

Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.