SPIO Nanoparticles Research Articles

Construction of magnetic drug delivery system and its potential application in tumor theranostics

Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.

SPIO nanoparticles and magnetic erythrocytes as contrast agents for biomedical and diagnostic applications

Superparamagnetic iron oxide nanoparticles (SPION) are available since many years and some of them are already approved for human use. New applications are currently emerging and the field is moving from the use of SPION as simply contrast agents, to more complex structures optimized in terms of core, size, shape and coating for different imaging modalities (e.g. MRI vs MPI), and different theranostic applications. Prof. Krishnan M. Kannan has greatly contributed to our understanding of the role of each of these parameters in shaping SPIO best function. Some of these developments are discussed in this short review just as examples. More recently, new cell-based SPIO constructs have also been optimized, moving the field from engineering the nanoparticles to the generation of hybrids cell-nanoparticle constructs. These developments have requested additional SPIO optimizations to maintain nanoparticles biocompatibility and properties and, at the same time, prevent cell damage and maintain cell functionality. Related examples from our lab are also discussed.

Hepatic and renal cellular cytotoxic effects of heparin-coated superparamagnetic Iron oxide nanoparticles

BackgroundSuperparamagnetic iron oxide (SPIO) nanoparticles have been widely used in several biomedical engineering in vivo. Although various surface modifications have been made to these non-biodegradable nanoparticles to make them more biocompatible, their toxic potential still remains a major concern.MethodIn this study, we newly developed unfractionated heparin (UFH)-coated and low molecular weight heparin (LMWH)-coated SPIO nanoparticles through surface modification engineering, which was compared with commercially available dextran-coated SPIO nanoparticles. Their toxicity such as cytotoxicity, single cell gel electrophoresis (SCGE) comet assay, intracellular reactive oxygen species (ROS) content and cellular apoptosis was evaluated to hepatic HepG2 and renal HK-2 cells.ResultsWhen UFH-, LMWH- or dextran-coated SPIO nanoparticles were applied, they did not affect the viability of HepG2 cell. However, HK-2 cells were more sensitive to dextran-coated SPIO nanoparticles than others. In genotoxicity assay using SCGE comet, DNA tail moment values in the groups treated with dextran- and LMWH-coated SPIO nanoparticles significantly increased. However, UFH-coated SPIO nanoparticles was only significantly lowing DNA tail moment value. In addition, UFH-coated SPIO nanoparticles had lower cytotoxicity in HepG2 and HK-2 cells compared to dextran-coated SPIO nanoparticles, especially in terms of apoptosis and intracellular ROS production.ConclusionsCollectively, it is possible that UFH- coated SPIO nanoparticles can be used as alternative negative contrast agents.

Anti-ST2 Nanoparticle Alleviates Lung Inflammation by Targeting ILC2s-CD4+T Response.

BackgroundAsthma has been regarded as an inflammatory disease, and group 2 innate lymphoid cells (ILC2s) are implicated in asthma pathogenesis. However, no strategy is available to block ILC2s function. Efficiency is also limited due to the use of systemic or subcutaneous routes of administration. The purpose of this study was to investigate the effects of nanoparticles targeting suppression of tumorigenicity 2 (ST2), which is the ILC2 receptor, to alleviate lung inflammation in the murine model of asthma.MethodsThe ultra-small SPIO nanoparticles were firstly synthesized, OVA-induced mice were administered by anti-ST2-conjugated nanoparticles. The inflammatory degree of the lung was investigated by H&E. The percentages of ILC2s and CD4+T cells in bronchoalveolar lavage fluid (BALF) and lung tissue were determined by FACS. Th2-cytokine and OVA-IgE levels were detected by real-time PCR and ELISA, respectively.ResultsTreatment with anti-ST2-conjugated nanoparticles significantly alleviated airway inflammation, IL-33 and IL-13 levels and the percentage of CD4+T cells. The percentage of ILC2s was increased, whereas the levels of IL-13 and IL-5 expressed by ILC2s were reduced.ConclusionIn the present study, we demonstrated that anti-ST2-conjugated nanoparticles can efficiently control lung inflammation in OVA-induced mice by reducing the ability of ILC2s to produce IL-5 and IL-13, thereby reducing CD4+T cells. Our study also demonstrated that the nanoparticle delivery system could improve the performance of anti-ST2, which may be used as a strategic tool to expand the current drug market.

Endocytic trafficking of polymeric clustered superparamagnetic iron oxide nanoparticles in mesenchymal stem cells

The technology of directing nanoparticles to specific locations in the body continues to be an area of great interest in a myriad of research fields. In the present study, we have developed nanoparticles and a method that allows the nanoparticles to move to specific sites by simultaneously utilizing the homing ability and magnetism of stem cells. Polymeric clustered SPIO (PCS) nanoparticles are composed of a superparamagnetic iron oxide nanoparticle (SPION) cluster core coated with poly lactic-co-glycolic acid (PLGA) and labeled with the fluorescent dye Cy5.5 for tracking. PCS is designed to be internalized by stem cells via endocytosis and then moved to the desired subcellular location through magnetism. Here, we investigated the interactions between SPIONs and mesenchymal stem cells (MSCs), including their absorption mechanism and subcellular localization. Exposure to the nanoparticles at 40 μg/mL for over 96 h did not affect cell survival or differentiation. We used a variety of endocytosis inhibitors and identified the potential cellular internalization pathway of SPIONs to be clathrin-mediated endocytosis. Antibodies to organelles were used to accumulate lysosomes through early and late endosomes. PCS at 40 μg/mL was internalized and stored without significant deleterious effects on stem cells, indicating that MSCs can act as an effective nanoparticle carrier. These findings also demonstrate the successful localization of the novel particles using magnetic attraction.

Antineoplastic drug-loaded polymer-modified magnetite nanoparticles: Comparative analysis of EPR-mediated drug delivery.

This study aimed to design and evaluate enhanced permeation and retention (EPR)-mediated anticancer effect of polymer-modified and drug-loaded magnetite nanocomposites. The preformulated bare (10 nm), chitosan-superparamagnetic iron oxide (SPIO; 69 nm), heparin-SPIO (42 nm), and (3-aminopropyl)triethoxysilane-polyethylene glycol-SPIO (17 nm) nanocomposites were utilized to evaluate the EPR-mediated localized cancer targeting and retention of doxorubicin (DOX) and paclitaxel (PTX) in human ovarian cancer cell lines, A2780 and OVCAR-3 in vitro and in the tumor-baring Balb/c mice in vivo. Fluorescence microscopy showed that DOX- and PTX-loaded SPIO nanoparticles caused long-term accumulation and cytoplasmic retention in A2780 and OVCAR-3 cells, as compared to free drugs in vitro. In vivo antiproliferative effect of present formulations on immunodeficient female Balb/c mice showed a tremendous amount of ovarian tumor shrinkage within 6 weeks. The present nanocomposite systems of targeted drug delivery proved to be efficient drug carrier with sustained drug release and long-term retention with enhanced cytotoxic properties in vitro and in vivo.

ENO1-targeted superparamagnetic iron oxide nanoparticles for detecting pancreatic cancer by magnetic resonance imaging.

The aim of this study was to investigate in vitro magnetic resonance imaging (MRI) of PDAC using ENO1‐targeted superparamagnetic iron oxide nanoparticles and xenograft models. Expression level and location of ENO1 protein in pancreatic cancer cell lines of CFPAC‐1 and MiaPaCa‐2 were detected by Western blotting, flow cytometry and confocal microscopy. Dex‐g‐PCL/SPIO nanoparticles targeting ENO1 were constructed with ENO1 antibody and characterized by MRI. In addition, ENO1‐Dex‐g‐PCL/SPIO nanoparticles were tested to assess their efficacy on the detection of PDAC using in vitro and in vivo MRI. The results showed that ENO1 was expressed in both human PDAC cell lines of CFPAC‐1 and MiaPaCa‐2, demonstrating that the localization of cytoplasm and membrane was dominant. It was confirmed that ENO1 antibody was connected to the SPIO surface in ENO1‐Dex‐g‐PCL/SPIO nanoparticles. The nanoparticles had satisfactory superparamagnetism and significantly enhance the detection of PDAC by in vivo and in vitro MRI. In conclusion, ENO1 can serve as a membrane protein expressed on human PDAC cell lines. ENO1‐targeted SPIO nanoparticles using ENO1 antibody can increase the efficiency of detection of PDAC by in vitro and in vivo MRI.

Mesoporous polydopamine carrying sorafenib and SPIO nanoparticles for MRI-guided ferroptosis cancer therapy

Iron-based nanomaterials as the main ferroptosis-inducing platforms are more promising because iron itself is a key component in the Fenton reaction to produce ROS. However, the Fe dose needs to be very high in order to induce ferroptosis-based cancer treatment using the SPIO NPs. Therefore, it is still of great challenge to enhance the efficacy of ferroptosis-based cancer therapy by associating the iron-based nanomaterials with other components and therapeutic modalities. In this study, sorafenib (SRF) and ultrasmall SPIO nanoparticles were loaded into the mesopores and onto the surface of MPDA NPs to form SRF@MPDA-SPIO nanoparticles. SPIO loading endowed the system with iron-supply for ferroptosis and made the system MRI-visible. Meanwhile, SRF was able to induce ferroptosis in cancer cells with lower Fe dose. Furthermore, the heat generated by MPDA NPs upon laser irradiation offered a moderate PTT to boost the ferroptosis effect. The SRF@MPDA-SPIO exhibited biocompatibility highly desirable for in vivo application and superior anticancer therapy via the combination of ferroptosis and photothermal therapy.

Tumor Cell Membrane-Based Peptide Delivery System Targeting to Tumor Microenvironment for Cancer Immunotherapy and Diagnosis

\The development of effective delivery system for peptides targeting to the tumor microenvironment has always been a hot topic in the field of cancer diagnosis and therapy. A multifunctional delivery system by encapsulating superparamagnetic iron oxide nanoparticles (SPIO NPs) with tumor cell membrane obtained by hypotonic lysis followed by mechanical fragmentation was constructed to effectively deliver therapeutic peptides. SPIO nanoparticles were encapsulated with H460 lung cancer cell membranes (SPIO NP@M) and peptides consisted of PD-L1 inhibitory peptide (TPP-1) and MMP2 substrate peptide (PLGLLG) was conjugated to H460 membrane (SPIO NP@M-P). The abilities of homologous targeting, cytotoxicity, pharmacokinetics, and tumor targeting ability of SPIO NP@M-P were evaluated. TPP-1 peptide was delivered and released to the tumor microenvironment through the homotypic effect of tumor cell membrane and specific digestion by the tumor specific enzyme, MMP2. The newly developed delivery system (SPIO NP@M-P) for PD-L1 inhibitory peptide could effectively extend the half-life of the peptides (60 times longer) and meanwhile maintain the ability to re-activate T cell and inhibit the tumor growth in vitro and in vivo. Furthermore, SPIO NPs in the system could be used as a tumor imaging agent and thus indicate the effect of peptide treatment. The SPIO NP@M might provide a promising theranostic platform for therapeutic peptide application in cancer therapy.

Localization of impalpable breast lesions and detection of sentinel lymph nodes through magnetic methods

PurposeThe most commonly used technique for guiding the surgical removal of impalpable breast lesions is wire-guided localization (WGL). Potential complications of WGL include wire migration, wire transection, patient discomfort, and pneumothorax. Recently, another possibility for preoperative localization of breast lesions trough small steel seeds was developed. A magnetic handheld probe can be used both for localization of breast lesions and sentinel lymph nodes (SLNs) detection. MethodsIn this study, we used a new technology for localizing breast lesions in conjunction with sentinel nodes (SLNs) detection through SPIO nanoparticles; both detected using a magnetic probe. The technique uses small steel markers (Magseed®) with magnetic properties, which are placed in breasts under ultrasonographic or mammographic guidance. 41 localization seeds were placed in 38 patients. In 27 patients with malignant tumors, simultaneous use of magnetic method for SLNs detection was used. ResultsIn all 38 patients, breast lesions were accurately localized using this method. No interference between Magseed signals and SPIO tracer signals were observed during magnetic probe measurements. All tumors were exscised with tumor-free surgical margins. The SLN biopsy was successful in all patients undergoing this procedure. The SLN median detection rate was 3 nodes. ConclusionsThe new magnetic methods are reliable alternatives for localizing breast lesions and SLN detection. They are well tolerated by patients and they can avoid the disadvantages of WGL. They have the potential to make tumor localization and SLN biopsy procedures possible in facilities without a nuclear medicine department or where radioisotope availability is limited.

Simultaneous use of magnetic method in localization of impalpable breast cancer and sentinel lymph nodes detection: initial experience.

In this study we used a new technology for localization of non-palpable breast tumors using a small steel marker in conjunction of sentinel nodes (SLNs) detection through injection of SPIO nanoparticles; both detected through a magnetic probe. Materials& methods: Ten patients with biopsy-proven nonpalpable invasive breast carcinoma or premalignant lesions eligible for SLNs biopsy were enrolled in this study. All tumors were removed with safe surgical margins. The mean nodal detection rate was 3.4 nodes per patient. No interferences in magnetic probe measurements due to the presence of both markers in the same breast were observed. Simultaneous use of the magnetic method in localization of impalpable breast tumors and SNs detection makes breast surgery convenient.

MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Insulin-producing cells (IPCs) derived from a patient’s own stem cells offer great potential for autologous transplantation in diabetic patients. However, the limited survival of engrafted cells remains a bottleneck in the application of this strategy. The present study aimed to investigate whether nanoparticle-based magnetic resonance (MR) tracking can be used to detect the loss of grafted stem cell-derived IPCs in a sensitive and timely manner in a diabetic monkey model. Pancreatic progenitor cells (PPCs) were isolated from diabetic monkeys and labeled with superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-labeled cells presented as hypointense signals on MR imaging (MRI). The labeling procedure did not affect the viability or IPC differentiation of PPCs. Importantly, the total area of the hypointense signal caused by SPION-labeled IPCs on liver MRI decreased before the decline in C-peptide levels after autotransplantation. Histological analysis revealed no detectable immune response to the grafts and many surviving insulin- and Prussian blue-positive cell clusters on liver sections at one year post-transplantation. Collectively, this study demonstrates that SPIO nanoparticles can be used to label stem cells for noninvasive, sensitive, longitudinal monitoring of stem cell-derived IPCs in large animal models using a conventional MR imager.

Polymer-brush-afforded SPIO Nanoparticles Show a Unique Biodistribution and MR Imaging Contrast in Mouse Organs.

Introduction:To investigate the biodistribution and retention properties of the new super paramagnetic iron oxide (new SPIO: mean hydrodynamic diameter, 100 nm) nanoparticles, which have concentrated polymer brushes in the outer shell and are difficult for phagocytes to absorb, and to compare the new SPIO with clinically approved SPIO (Resovist: mean hydrodynamic diameter, 57 nm).Materials and Methods:16 male C57BL/6N mice were divided in two groups according to the administered SPIO (n = 8 for each group; intravenous injection does, 0.1 ml). In vivo magnetic resonance imaging (MRI) was performed before and one hour, one day, one week and four weeks after SPIO administration by two dimensional-the fast low angle shot (2D-FLASH) sequence at 11.7T. Ex vivo high-resolution images of fixed organs were also obtained by (2D-FLASH). After the ex vivo MRI, organs were sectioned and evaluated histologically to confirm the biodistribution of each particle precisely.Results:The new SPIO was taken up in small amounts by liver Kupffer cells and showed a unique in vivo MRI contrast pattern in the kidneys, where the signal intensity decreased substantially in the boundaries between cortex and outer medulla and between outer and inner medulla. We found many round dark spots in the cortex by ex vivo MRI in both groups. Resovist could be detected almost in the cortex. The shapes of the dark spots were similar to those observed in the new SPIO group. Transmission electron microscopy revealed that Resovist and the new SPIO accumulated in different cells of glomeruli, that is, endothelial and mesangial cells, respectively.Conclusion:The new SPIO was taken up in small amounts by liver tissue and showed a unique MRI contrast pattern in the kidney. The SPIO were found in the mesangial cells of renal corpuscles. Our results indicate that the new SPIO may be potentially be used as a new contrast agent for evaluation of kidney function as well as immunune function.

Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity

Superparamagnetic iron oxide nanoparticles (SPIONs) are highly cytotoxic and target cancer cells with high specificity; however, the mechanism by which SPIONs induce cancer cell-specific cytotoxicity remains unclear. Herein, the molecular mechanism of SPION-induced cancer cell-specific cytotoxicity to cancer cells is clarified through DNA microarray and bioinformatics analyses. SPIONs can interference with the mitochondrial electron transport chain (METC) in cancer cells, which further affects the production of ATP, mitochondrial membrane potential, and microdistribution of calcium, and induces cell apoptosis. Additionally, SPIONs induce the formation of reactive oxygen species in mitochondria; these reactive oxygen species trigger cancer-specific cytotoxicity due to the lower antioxidative capacity of cancer cells. Moreover, the DNA microarray and gene ontology analyses revealed that SPIONs elevate the expression of metallothioneins in both normal and cancer cells but decrease the expression of METC genes in cancer cells. Overall, these results suggest that SPIONs induce cancer cell death by targeting the METC, which is helpful for designing anti-cancer nanotheranostics and evaluating the safety of future nanomedicines.

First demonstration of RF pulse pEPR detection system for SPIO nanoparticles

The first demonstration of a pulsed electron paramagnetic resonance (EPR) detection system based on the recently announced particle EPR (pEPR) technology for superparamagnetic iron oxide nanoparticles (SPIONs) applications is presented. The SPIONs have large magnetisation, which allows one to detect the electron resonance under a low magnetic field and at room temperature. However, the broad linewidth of the superparamagnetic particles leads to a short relaxation time which requires a quick damping of the transmit signal. The presented experiments on a commercial SPION prove the feasibility to detect a pulsed electron response from broad linewidth particles using the pulsed pEPR technology.

Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

Effect of MRI tags: SPIO nanoparticles and 19F nanoemulsion on various populations of mouse mesenchymal stem cells

Transplantation of mesenchymal stem cells (MSCs) has emerged as a promising strategy for the treatment of myriad human disorders, including several neurological diseases. Superparamagnetic iron oxide nanoparticles (SPION) and fluorine nanoemulsion (19F) are characterized by low toxicity and good sensitivity, and, as such, are among the most frequently used cell-labeling agents. However, to date, their impact across the various populations of MSCs has not been comprehensively investigated. Thus, the impact of MRI tags (independent variable) has been set as a primary endpoint. The various populations of mouse MSCs in which the effect of tag was investigated consisted of (1) tissue of cell origin: bone marrow vs. Adipose tissue; (2) age of donor: young vs. old; (3) cell culture conditions: hypoxic vs. normal vs. normal + ascorbic acid (AA); (4) exposure to acidosis: yes vs. no. The impact of those populations has been also analyzed and considered as secondary endpoints. The experimental readouts (dependent variables) included: (1) cell viability; (2) cell size; (3) cell doubling time; (4) colony formation; (5) efficiency of labeling; and (6) cell migration. We did not identify any impact of cell labeling for these investigated populations in any of the readouts. In addition, we found that the harsh microenvironment of injured tissue modeled by a culture of cells in a highly acidic environment has a profound effect on all readouts, and both age of donor and cell origin tissue also have a substantial influence on most of the readouts, while oxygen tension in the cell culture conditions has a smaller impact on MSCs. A detailed characterization of the factors that influence the quality of MSCs is vital to the proper pursuit of preclinical and clinical studies.

Preferential Macrophage Recruitment and Polarization in LPS-Induced Animal Model for COPD: Noninvasive Tracking Using MRI

Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of chronic obstructive respiratory diseases (COPD), which make them attractive vehicles to deliver contrast agents for diagnostic or drugs for therapeutic purposes. This study was designed to monitor and evaluate the migration of differently polarized M1 and M2 iron labeled macrophage subsets to the lung of a LPS-induced COPD animal model and to assess their polarization state once they have reached the inflammatory sites in the lung after intravenous injection. Ex vivo polarized bone marrow derived M1 or M2 macrophages were first efficiently and safely labeled with amine-modified PEGylated dextran-coated SPIO nanoparticles and without altering their polarization profile. Their biodistribution in abdominal organs and their homing to the site of inflammation in the lung was tracked for the first time using a free-breathing non-invasive MR imaging protocol on a 4.7T magnet after their intravenous administration. This imaging protocol was optimized to allow both detection of iron labeled macrophages and visualization of inflammation in the lung. M1 and M2 macrophages were successfully detected in the lung starting from 2 hours post injection with no variation in their migration profile. Quantification of cytokines release, analysis of surface membrane expression using flow cytometry and immunohistochemistry investigations confirmed the successful recruitment of injected iron labeled macrophages in the lung of COPD mice and revealed that even with a continuum switch in the polarization profile of M1 and M2 macrophages during the time course of inflammation a balanced number of macrophage subsets predominate.

The effect of superparamagnetic iron oxide with iRGD peptide on the labeling of pancreatic cancer cells in vitro: a preliminary study.

The iRGD peptide loaded with iron oxide nanoparticles for tumor targeting and tissue penetration was developed for targeted tumor therapy and ultrasensitive MR imaging. Binding of iRGD, a tumor homing peptide, is mediated by integrins, which are widely expressed on the surface of cells. Several types of small molecular drugs and nanoparticles can be transfected into cells with the help of iRGD peptide. Thus, we postulate that SPIO nanoparticles, which have good biocompatibility, can also be transfected into cells using iRGD. Despite the many kinds of cell labeling studies that have been performed with SPIO nanoparticles and RGD peptide or its analogues, only a few have applied SPIO nanoparticles with iRGD peptide in pancreatic cancer cells. This paper reports our preliminary findings regarding the effect of iRGD peptide (CRGDK/RGPD/EC) combined with SPIO on the labeling of pancreatic cancer cells. The results suggest that SPIO with iRGD peptide can enhance the positive labeling rate of cells and the uptake of SPIO. Optimal functionalization was achieved with the appropriate concentration or concentration range of SPIO and iRGD peptide. This study describes a simple and economical protocol to label panc-1 cells using SPIO in combination with iRGD peptide and may provide a useful method to improve the sensitivity of pancreatic cancer imaging.

Folic acid-conjugated glucose and dextran coated iron oxide nanoparticles as MRI contrast agents for diagnosis and treatment response of rheumatoid arthritis.

Coating superparamagnetic iron oxide (SPIO) with dextran increases the stability of the magnetic nanoparticles during blood circulation, yet this is accompanied by an increase in the particle size and the vascular permeability efficiency of the SPIO nanoparticles into the joints decreases. In our study, the thickness of the dextran coated onto SPIO (dex-SPIO) was optimized without affecting the magnetic quality of iron oxide by adding a suitable amount of glucose into the crystal growth process. To further improve the signal enhancement effect of this glucose and dextran coated SPIO (glu-dex-SPIO) for the detection of the inflammatory site of arthritis, folic acid (FA) was conjugated to glu-dex-SPIO. This FA glu-dex-SPIO was used as a negative contrast agent for MRI to visualize the antigen induce arthritis (AIA) model in rats using a 7 T MR scans. MR imaging revealed more significant differences between the synovium and surrounding tissues with FA glu-dex SPIO than when using the non-targeting glu-dex-SPIO over a long period of time (24 h) after intravenous injection. Moreover, the therapeutic efficacy of the cyclooxygenase 2 (COX-2) inhibitor treatment of the inflamed joints also could be confirmed by using FA glu-dex SPIO enhanced MRI, indicating that this type of nanoparticles could also have potential as a contrast agent for measuring the treatment response of rheumatoid arthritis.