Surface Of Superparamagnetic Iron Oxide Research Articles

Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and −45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

Surface modification of superparamagnetic iron oxide (SPION) and comparison of cytotoxicity effect of mPEG2000-PEI-SPION and mPEG750-PEI-SPION on the human embryonic carcinoma stem cell, NTERA2 cell line.

Non-viral carriers based on nanoparticles are promising vectors for drug and gene delivery into the target cells. The data provided in this article are related to research entitled "Efficiency of surface modified SPION". In this article the surface of superparamagnetic iron oxide (SPION) (core) coated with poly (ethylene glycol)-grafted polyethylenimine (mPEG-co-PEI) shell. PEI was used to increase gene transfection efficiency and poly (ethylene glycol) methyl ether was applied to reduce cytotoxicity of nanoparticles, because our goal is that two sets of mPEG-co-PEI coated SPIONs (mPEG-750 and 2000) were prepared as carrier for the purpose of gene delivery. Structure of the mPEG-co-PEI product was elucidate by using 1H-NMR spectroscopy. Physicochemical features of the modified-SPIONs were evaluated by zeta-potential analysis. Cytotoxic effect of Nano carries were then assayed by MTT in NT2 cell line. Data analyzed by excel and p< 0.05 was considered significant. Finally siRNA absorption Ability of mPEG750-PEI-SPION and mPEG2000-PEI-SPION was tested by N/P ratio test (gel retardation assay). Our data shown that mPEG750-G-Pei-Spion and mPEG2000-G-Pei-Spion were non-toxic up to 100μg/ml in vitro for NT2 cell line.

Mn(ii) chelate-coated superparamagnetic iron oxide nanocrystals as high-efficiency magnetic resonance imaging contrast agents.

In this communication, a paramagnetic bifunctional manganese(ii) chelate ([Mn(Dopa-EDTA)]2−) containing a catechol group is designed and synthesized. The catechol can bind iron ions on the surface of superparamagnetic iron oxide (SPIO) nanocrystals to form core–shell nanoparticles. Both 4 and 7 nm SPIO@[Mn(Dopa-EDTA)]2− show good water solubility, single-crystal dispersion, and low cytotoxicity. The study of the interplay between the longitudinal and transverse relaxation revealed that 4 nm SPIO@[Mn(Dopa-EDTA)]2− with lower r2/r1 = 1.75 at 0.5 T tends to be a perfect T1 contrast agent while 7 nm SPIO@[Mn(Dopa-EDTA)]2− with a higher r2/r1 = 15.0 at 3.0 T tends to be a T2 contrast agent. Interestingly, 4 nm SPIO@[Mn(Dopa-EDTA)]2− with an intermediate value of r2/r1 = 5.26 at 3.0 T could act as T1–T2 dual-modal contrast agent. In vivo imaging with the 4 nm SPIO@[Mn(Dopa-EDTA)]2− nanoparticle shows unique imaging features: (1) long-acting vascular imaging and different signal intensity changes between the liver parenchyma and blood vessels with the CEMRA sequence; (2) the synergistic contrast enhancement of hepatic imaging with the T1WI and T2WI sequence. In summary, these Fe/Mn hybrid core–shell nanoparticles, with their ease of synthesis, good biocompatibility, and synergistic contrast enhancement ability, may provide a useful method for tissue and vascular MR imaging.

A Combinatorial Approach for the Fabrication of Magneto-Optical Hybrid Nanoparticles.

IntroductionThe increasing demands for better resolution combined with anatomical information in biomedical imaging necessitate the development of multimodal contrast agents. In this respect, the multivalency of nanotechnology enables the integration of nanomaterials with distinct biophysical properties into a unique probe, capable to exert superior imaging characterstics through synergistic enhancement unmatched by any single modality.Materials and methodsNovel magneto-optical hybrid nanoparticles (MOHNPs), comprise semiconductor quantum dots (QDs) tethered on the surface of superparamagnetic iron oxide (SPIO) NPs, were synthesized using a combinatorial approach. The semiconductor components utilized for the synthesis of the hybrid NPs contained cadmium-free QDs, which were stabilized by a variety of functional ligands including thiols, polyethyleneimine (PEI) and amphiphilic polymers. While SPIO NPs were further modified with silica or PEI on the outermost layer. The main mechanism to assemble semiconductor QDs onto the SPIO NPs employed a core-shell approach, in which covalent bonding and electrostatic interaction held the components together.ResultsThe versatility of the NP assembling mechanism described in this work offered a robust and flexible fabrication of MOHNPs. A proof-of-concept study demonstrated desterous coating of folic acid onto the surface of MOHNPs to create a targeted imaging probe. The emission of the resulted hybrid NPs extended in the near-infrared region, suitable for in vivo applications.ConclusionThis novel assembling technology offers far-reaching capabilities to generate complex multimodal nanoiamging probes.

Preparation and characterization of alginate based-fluorescent magnetic nanoparticles for fluorescence/magnetic resonance multimodal imaging applications

Simple and versatile methodologies have been reported that customize the surface of superparamagnetic iron oxide (SPIO) nanoparticles and impart additional fluorescence capabilities to these contrast agents. Herein, we present the rational design, synthesis, characterization, and biological applications of a new magnetic-based fluorescent probe. The dual modality imaging protocol was developed by labeling fluorophore with alginate natural polymers that have excellent biocompatibility and biodegradability, and using gelification method to form nanocomposites containing SPIO. The formation of alginate-based fluorescent magnetic (AFM) nanoparticles was observed in spherical and elliptical forms with a diameter of less than 500 nm by a transmission electron microscope (TEM). The fluorescent wavelength band in the range of 560 nm was also confirmed in the UV–visible spectrophotometer. In this study, we demonstrate that the multi-tasking design of AFM nanoparticles provides an ideal platform for building balanced dual-image probes of magnetic resonance imaging and optical imaging.

Synthesis of a cell penetrating peptide modified superparamagnetic iron oxide and MRI detection of bladder cancer.

Bladder cancer is the most common malignancy of the urinary tract for which the accurate measurement of minimal residual disease is critical to treatment and determining prognosis. Although cystoscope examination and voided urine cytology remain the current standard of care for detecting residual disease, these approaches are limited by mechanical trauma and lack sensitivity. To develop a new accurate noninvasive method, we developed a novel contrast agent where the surface of superparamagnetic iron oxide (SPIO) nanoparticles is functionalized with a bladder cancer-specific fluorescein isothiocyanate (FITC) labeled cell penetrating peptide (CPP)-polyarginine peptides (R11) for active targeting and imaging. The stable nanoparticles have an average hydrodynamic diameter of 51 nm, surface charge of -21 mV and MRI r2 relaxivity 135 mM−1s−1. In vitro cell studies demonstrated that the R11-conjugated SPIO (SPIO-R11) nanoparticles were taken up by bladder cancer cells (T24) in a dose-dependent manner, which was higher than unconjugated SPIO. TEM showed that SPIO-R11 was mainly concentrated on cell vesicle and lysosome, not in cell nucleus, and no obvious damage was seen on cell ultrastructure. Moreover, uptake of the nanoparticles showed significantly more SPIO-R11 accumulation in bladder cancer cells than in immortalized bladder epithelial cells unlike control SPIO. Further, SPIO-R11 was compatible with immortalized bladder epithelial cells at all tested concentrations up to 200 μg/mL after 72 h incubation. Moreover, SPIO-R11 decreased the magnetic resonance T2 relaxation time by 73% in tumors cells in vitro compared to 12% with SPIO. These results indicate great potential of SPIO-R11 as contrast agent to target bladder cancer for diagnostic and therapeutic applications.

Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r1) (r2/r1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats.

Catch and release with DNA by imidazolium-presenting iron oxide nanoparticles via anion exchange

We present the catch and release technique with DNA using imidazolium-presenting nanoparticles via anion exchange. The imidazolium-tethered superparamagnetic iron oxide (SPIO) was prepared and the binding behavior to DNA was investigated. Accordingly, when the imidazolium cation forms an ion pair with the hydrophilic anion such as chloride, DNA can be absorbed onto the modified SPIO. In contrast, by anion exchange to hydrophobic anion such as TFSA−, the binding affinity greatly decreased, resulting in the release of DNA. Moreover, the release efficiency can be improved by introducing a silica layer at the surface of SPIOs. Finally, the catch and release with DNA was accomplished under mild conditions.

Mono and dialkoxysilane surface modification of superparamagnetic iron oxide nanoparticles for application as magnetic resonance imaging contrast agents

Abstract

Magnetic resonance imaging using heparin-coated superparamagnetic iron oxide nanoparticles for cell tracking in vivo.

Magnetic resonance imaging (MRI) is a tremendous modality for noninvasive cell tracking. To this end, superparamagnetic iron oxide (SPIO), one of the MRI contrast agents, should be labeled to the cells before transplantation. Currently, cellular labelling with SPIOs such as Feridex and Resovist is generally carried out through their engulfment into cytosol via endocytosis. However, the labelling efficacy via endocytosis is relatively low due to their non-specific random engulfment and degradation in the cytosol. To overcome these limitations, transfection agents such as poly-L-lysine and lipofectamine are complexed with SPIOs and treated to the cells. However, these strategies should be optimized due to the cytotoxicity of transfection agents themselves. Recently, there were developments of chemical conjugation of SPIOs onto cellular membrane. To this end, the surface of SPIOs was coated with heparin polysaccharide and chemically conjugated with collagen matrix layer of cell surface by using linker polymer, which was stably maintained in vivo. This new remedy can overcome the limitations of cell labelling via endocytosis. Collectively, these strategies could be applied for noninvasive imaging of MRI after cell transplantation in vivo.

A Facile Approach to Fabricate Water‐soluble Au‐Fe3O4 Nanoparticle for Liver Cancer Cells Imaging

AbstractAu‐Fe3O4 nanoparticles were widely used as nanoplatforms for biologic applications through readily further functionalization. Dopamine (DA)‐coated superparamagnetic iron oxide (SPIO) nanoparticles (DA@Fe3O4) have been successfully synthesized using a one‐step process by modified coprecipitation method. Then 2–3 nm gold nanoparticles were easily conjugated to DA@Fe3O4 nanoparticles by the electrostatic force between gold nanoparticles and amino groups of dopamine to afford water‐soluble Au‐Fe3O4 hybrid nanoparticles. A detailed investigation by dynamic light scatting (DLS), transmission electron microscopy (TEM), fourier transform infrared (FT‐IR) and X‐ray diffraction (XRD) were performed in order to characterize the physicochemical properties of the hybrid nanoparticles. The hybrid nanoparticles were easily functionalized with a targeted small peptide A54 (AGKGTPSLETTP) and fluorescence probe fluorescein isothiocyanate (FITC) for liver cancer cell BEL‐7402 imaging. This simple approach to prepare hybrid nanoparticles provides a facile nanoplatform for muti‐functional derivations and may be extended to the immobilization of other metals or bimolecular on SPIO surface.

Synthesis and functionalization of magnetite nanoparticles with different amino-functional alkoxysilanes

Superparamagnetic iron oxide (SPIO) nanoparticles show great promise for many biotechnological applications. This paper addresses the synthesis and characterization of SPIO nanoparticles grafted with three different alkoxysilanes: 3-aminopropyl-triethoxysilane (APTES), 3-aminopropyl-ethyl-diethoxysilane (APDES) and 3-aminopropyl-diethy-ethoxysilane (APES). SPIO nanoparticles with an average particle diameter of 10nm were prepared by chemical sonoprecipitation. As confirmed by Fourier transform infrared (FTIR) spectroscopy, silylation of these nanoparticles occurs through a two-step process. Decreasing the number of alkoxide groups reduced the concentration of free amino groups on the SPIO surface ([SPIO-NH2]—APTES>APDES>APES). This phenomenon results from steric contributions and the formation of H-bonded amines provided by the ethyl groups present in the APDES and APES molecules. A simulation of SPIO nanoparticles in a saline physiologic solution shows that the ethyl groups impart larger steric stability onto the ferrofluids, which reduces aggregation. The magnetization (M) versus magnetic field (H) curves show that the synthesized iron oxide nanoparticles display superparamagnetic behavior. The zero-field cooling (ZFC) and field cooling (FC) curves show that the changes in the blocking temperature depend on the alkoxysilane-functionalized particle surface.

Highly effective T2 MR contrast agent based on heparinized superparamagnetic iron oxide nanoparticles

In this study a potential magnetic resonance (MR) T2 contrast agent was developed systematically based on heparin-coated superparamagnetic iron oxide (SPIO) nanoparticles. Dextran-coated SPIO, which is commercially available as Feridex®, was prepared for the control group. The size of the crystalline core was adjusted to provide suitable relaxometric properties. Compared to the uncoated SPIO, the heparin or dextran coating provided a better dispersion of SPIO nanoparticles in solution. The zeta potential of the SPIO surface was detected to confirm the polymer coating. The Zeta potential of non-coated SPIO was approximatelt −44 mV, whereas dextran-coated or heparin-coated SPIO was −6.4 and −33.5 mV, respectively. The zeta potential of heparin-coated SPIO was caused by the rich sulfonate group of heparin. In addition, the heparin-coated SPIO showed higher hyponegativity than dextran-coated SPIO. The reason was that the heparin-coated had a lower r2/r1 ratio (18.2) at 1.5-T magnetic resonance imaging (MRI) compared to dextran-coated SPIO (r2/r1 ratio 32.9). Both SPIO nanoparticles can be still suitable for T2-weighted MRI because r2/r1 ratio was >10. From the results of in vitro cellular labeling, heparin-coated SPIO was more advantageous for cellular labeling because it could powerfully visualize the cells after a short incubation time (2 h). From these findings, it is possible that heparin-coated SPIO can be used as a good negative contrast agent in clinical MRI.

99mTc-Bisphosphonate-Iron Oxide Nanoparticle Conjugates for Dual-Modality Biomedical Imaging

The combination of radionuclide-based imaging modalities such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) with magnetic resonance imaging (MRI) is likely to become the next generation of clinical scanners. Hence, there is a growing interest in the development of SPECT- and PET-MRI agents. To this end, we report a new class of dual-modality imaging agents based on the conjugation of radiolabeled bisphosphonates (BP) directly to the surface of superparamagnetic iron oxide (SPIO) nanoparticles. We demonstrate the high potential of BP-iron oxide conjugation using (⁹⁹m)Tc-dipicolylamine(DPA)-alendronate, a BP-SPECT agent, and Endorem/Feridex, a liver MRI contrast agent based on SPIO. The labeling of SPIOs with (⁹⁹m)Tc-DPA-alendronate can be performed in one step at room temperature if the SPIO is not coated with an organic polymer. Heating is needed if the nanoparticles are coated, as long as the coating is weakly bound as in the case of dextran in Endorem. The size of the radiolabeled Endorem (⁹⁹m)Tc-DPA-ale-Endorem) was characterized by TEM (5 nm, Fe₃O₄ core) and DLS (106 ± 60 nm, Fe₃O₄ core + dextran). EDX, Dittmer-Lester, and radiolabeling studies demonstrate that the BP is bound to the nanoparticles and that it binds to the Fe₃O₄ cores of Endorem, and not its dextran coating. The bimodal imaging capabilities and excellent stability of these nanoparticles were confirmed using MRI and nanoSPECT-CT imaging, showing that (⁹⁹m)Tc and Endorem co-localize in the liver and spleen In Vivo, as expected for particles of the composition and size of (⁹⁹m)Tc-DPA-ale-Endorem. To the best of our knowledge, this is the first example of radiolabeling SPIOs with BP conjugates and the first example of radiolabeling SPIO nanoparticles directly onto the surface of the iron oxide core, and not its coating. This work lays down the basis for a new generation of SPECT/PET-MR imaging agents in which the BP group could be used to attach functionality to provide targeting, stealth/stability, and radionuclides to Fe₃O₄ nanoparticles using very simple methodology readily amenable to GMP.

Modification of MR molecular imaging probes with cysteine‐terminated peptides and their potential for in vivo tumour detection

One of the challenges facing superparamagnetic iron oxide (SPIO) nanoparticles is to improve their biological compatibility. While highly uniform SPIOs can be manufactured, the surfaces are hydrophobic as a result of the surfactants used in their fabrication. In this study, we developed a general strategy to fabricate an MR molecular imaging probe in one step by replacing hydrophobic surfactants with small peptides terminated with cysteine. The hydrophobic SPIO surface was transformed into a hydrophilic one by exchanging surface oleic acids with the peptides RGD-Cys or RGD-PEG-Cys. After the RGD-Cys and RGD-PEG-Cys peptide exchange, both RGD-Cys-SPIO and RGD-PEG-Cys-SPIO specifically targeted α(v)β(3)-expressing cells (A549) in vitro, with RGD-Cys-SPIO achieving this more efficiently. Furthermore, MR imaging of A549 tumors receiving RGD-Cys-SPIO or RGD-PEG-Cys-SPIO demonstrated that both the targeted particles could reach and label the α(v)β(3)-expressing tumor, much more efficiently than the non-targeted particles (Cys-SPIO). Histology showed that the probes not only target the tumor neovasculature but also extravasate from vessels and address the tumor cells. Our study shows that directly replacing oleic acid with cysteine or cysteine-terminated small peptides is a general strategy to transforming the hydrophobic surface of SPIO into a hydrophilic one, as well as providing targeting ligands. Such SPIOs are of interest as MR molecular imaging probes to detect for cancer in vivo.

Facilitated Monocyte-Macrophage Uptake and Tissue Distribution of Superparmagnetic Iron-Oxide Nanoparticles

BackgroundWe posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.MethodsMonocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was synthesized by covalent linkage and uptake into monocytes and MDM investigated related to size, time, temperature, concentration, and coatings. SPIO and IgG SPIO were infused intravenously into naïve mice. T2 measures using magnetic resonance imaging (MRI) were used to monitor tissue distribution in animals.ResultsOxidation of dextran on the SPIO surface generated reactive aldehyde groups and permitted covalent linkage to amino groups of murine and human IgG and F(ab')2 fragments and for Alexa Fluor® 488 hydroxylamine to form a Schiff base. This labile intermediate was immediately reduced with sodium cyanoborohydride in order to stabilize the NP conjugate. Optical density measurements of the oxidized IgG, F(ab')2, and/or Alexa Fluor® 488 SPIO demonstrated ∼50% coupling yield. IgG-SPIO was found stable at 4°C for a period of 1 month during which size and polydispersity index varied little from 175 nm and 200 nm, respectively. In vitro, NP accumulated readily within monocyte and MDM cytoplasm after IgG-SPIO exposure; whereas, the uptake of native SPIO in monocytes and MDM was 10-fold less. No changes in cell viability were noted for the SPIO-containing monocytes and MDM. Cell morphology was not changed as observed by transmission electron microscopy. Compared to unconjugated SPIO, intravenous injection of IgG-SPIO afforded enhanced and sustained lymphoid tissue distribution over 24 hours as demonstrated by MRI.ConclusionsFacilitated uptake of coated SPIO in monocytes and MDM was achieved. Uptake was linked to particle size and was time and concentration dependent. The ability of SPIO to be rapidly taken up and distributed into lymphoid tissues also demonstrates feasibility of macrophage-targeted nanoformulations for diagnostic and drug therapy.

Enhanced Cell Uptake of Superparamagnetic Iron Oxide Nanoparticles Functionalized with Dendritic Guanidines

Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of disease and the study of biological processes such as cancer metastasis and inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been shown to be effective contrast agents for labeling cells to provide high sensitivity in MRI, but this sensitivity depends on the ability to label cells with sufficient quantities of SPIO, which can be challenging for nonphagocytic cells such as cancer cells. To address this issue, a novel cell-penetrating polyester dendron with peripheral guanidines was developed and conjugated to the surface of SPIO. The functionalized nanoparticles were characterized by transmission electron microscopy, infrared spectroscopy, and dynamic light scattering, and it was found that the surface functionalization reaction proceeded to completion and did not have any adverse effects on the SPIO. In GL261 mouse glioma cells, the dendritic guanidine exhibited remarkably similar cell-penetrating capabilities to the HIV-Tat(47-57) peptide for the transport of fluorescein, and when conjugated to SPIO, it provided significantly enhanced uptake in comparison with nanoparticles having no dendron or dendrons with hydroxyl or amine peripheries. This uptake led to substantial decreases in the transverse relaxation time (T(2)) of labeled cells relative to control cells. While the nanoparticles functionalized with dendritic guanidines exhibited somewhat greater toxicity than those functionalized with dendrons having hydroxyl or amine peripheries, they were still relatively nontoxic at the low concentrations required for labeling.