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1.
The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.  相似文献   

2.
目的 油酸改性超顺磁性氧化铁纳米粒子(O-SPION)被应用于制备高品质的MRI T2阴性造影剂或搭载药物的磁靶向分子探针,不同于传统的物理合成方法,本课题组尝试采过化学方法制备O-SPION,并通过体外实验检测其细胞毒性及细胞透过性。方法 通过共沉淀法制备分散性好、磁响应强的超顺磁性纳米粒子。对油酸的羧基进行活化后,利用缩合反应实现油酸改性SPION的化学合成。采用X-Ray衍射仪、红外光谱仪、激光粒度分布测试仪、透射电镜对产物进行表征。MTT法检测其对人肝癌细胞HepG2的毒性作用,普鲁士蓝染色检测其细胞摄取能力。结果 O-SPION的核心粒径为12?.5 nm的,其具有稳定的化学结构和低表面电势,体外实验证明其低毒或无毒性,且在细胞内的摄取量较原始SPION明显增多。结论 利用化学方法成功合成了O-SPION,为进一步制备高品质MRI造影剂提供实验依据。  相似文献   

3.
This study aims to fabricate and formulate a new magnetic resonance imaging (MRI) contrast agent based on a dextran?Cspermine nanoparticulate system loaded with super paramagnetic iron oxide nanoparticles (SPION). SPION-loaded spermine?Cdextran nanoparticles were prepared according to a procedure based on the ionic gelation of dextran?Cspermine with sodium tripolyphosphate (TPP) anions. The effects of process parameters such as pH, concentration of spermine dextran, TPP to dextran?Cspermine and SPION to dextran?Cspermine weight ratios, and TPP addition rate were fully investigated to find the optimized formulation through the response surface methodology. At the optimum condition, 75% of the magnetic iron oxide nanoparticles added to the polymeric solution were entrapped in dextran?Cspermine nanoparticles. Samples were investigated by transmission electron microscopy. The mean particle size of the nanoparticles determined by particle size analyzer was found to be 65?nm at the optimum condition with zeta potential of +90?mV. The SPION-loaded dextran?Cspermine nanoparticle formulation has the same superparamagnetic properties as SPIONs and at same iron concentration the saturation magnetization (Ms) of the SPION-loaded dextran?Cspermine nanoparticles was larger than SPIONs. In vitro MRI was performed with gradient echo and spin-echo sequences at 1.5?T. By increasing of iron concentration, the T 2 relaxation times were reduced. Thus, indicating that the saturation magnetization and r 2 and $ r_{2}^{*} $ relaxivities were enhanced, and the contrast effects were improved in comparison to commercial SPIONs.  相似文献   

4.
Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications.  相似文献   

5.
Surface engineering of iron oxide nanoparticles for targeted cancer therapy   总被引:2,自引:0,他引:2  
Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired response. Of the nanomaterials studied, iron oxide nanoparticles have emerged as one of top candidates for cancer therapy. Their intrinsic superparamagnetism enables noninvasive magnetic resonance imaging (MRI), and their biodegradability is advantageous for in vivo applications. A therapeutic superparamagnetic iron oxide nanoparticle (SPION) typically consists of three primary components: an iron oxide nanoparticle core that serves as both a carrier for therapeutics and contrast agent for MRI, a coating on the iron oxide nanoparticle that promotes favorable interactions between the SPION and the biological system, and a therapeutic payload that performs the designated function in vivo. Often, the design may include a targeting ligand that recognizes the receptors over-expressed on the exterior surface of cancer cells. The body is a highly complex system that imposes multiple physiological and cellular barriers to foreign objects. Thus, the success of a therapeutic SPION largely relies on the design of the iron oxide core to ensure its detection in MRI and the coatings that allow the nanoparticles to bypass these barriers. Strategies to bypass the physiological barriers, such as liver, kidneys, and spleen, involve tuning the overall size and surface chemistry of the SPION to maximize blood half-life and facilitate the navigation in the body. Strategies to bypass cellular barriers include the use of targeting agents to maximize uptake of the SPION by cancer cells and the employment of materials that promote desired intracellular trafficking and enable controlled drug release. The payload can be genes, proteins, chemotherapy drugs, or a combination of these molecules. Each type of therapeutic molecule requires a specific coating design to maximize the loading and to achieve effective delivery and release. In this Account, we discuss the primary design parameters in developing therapeutic SPIONs with a focus on surface coating design to overcome the barriers imposed by the body's defense system. We provide examples of how these design parameters have been implemented to produce SPIONs for specific therapeutic applications. Although there are still challenges to be addressed, SPIONs show great promise in the successful diagnosis and treatment of the most devastating cancers. Once the critical design parameters have been optimized, these nanoparticles, combined with imaging modalities, can serve as truly multifunctional theranostic agents that not only perform a therapeutic function but also provide instant clinical feedback, allowing the physician to adjust the treatment plan.  相似文献   

6.
Magnetic nanoparticle systems can be divided into single-core nanoparticles (with only one magnetic core per particle) and magnetic multi-core nanoparticles (with several magnetic cores per particle). Here, we report multi-core nanoparticle synthesis based on a controlled precipitation process within a well-defined oil in water emulsion to trap the superparamagnetic iron oxide nanoparticles (SPION) in a range of polymer matrices of choice, such as poly(styrene), poly(lactid acid), poly(methyl methacrylate), and poly(caprolactone). Multi-core particles were obtained within the Z-average size range of 130 to 340 nm. With the aim to combine the fast room temperature magnetic relaxation of small individual cores with high magnetization of the ensemble of SPIONs, we used small (<10 nm) core nanoparticles. The performed synthesis is highly flexible with respect to the choice of polymer and SPION loading and gives rise to multi-core particles with interesting magnetic properties and magnetic resonance imaging (MRI) contrast efficacy.  相似文献   

7.
Magnetically labelled cells are used for in vivo cell tracking by MRI, used for the clinical translation of cell-base therapies. Studies involving magnetic labelled cells may include separation of labelled cells, targeted delivery and controlled release of drugs, contrast enhanced MRI and magnetic hyperthermia for the in situ ablation of tumours. Dextran-coated super-paramagnetic iron oxide (SPIO) ferumoxides are used clinically as an MR contrast agents primarily for hepatic imaging. The material is also widely used for in vitro cell labelling, as are other SPIO-based particles. Our results on the uptake by human cancer cell lines of ferumoxides indicate that electroporation in the presence of protamine sulphate (PS) results in rapid high uptake of SPIO nanoparticles (SPIONs) by parenchymal tumour cells without significant impairment of cell viability. Quantitative determination of cellular iron uptake performed by colorimetric assay is in agreement with data from the literature. These results on intracellular iron content together with the intracellular distribution of SPIONs by magnetic force microscopy (MFM) following in vitro uptake by parenchymal tumour cells confirm the potential of this technique for clinical tumour cell detection and destruction.  相似文献   

8.
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.  相似文献   

9.
Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEONLA-BSA, which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEONLA-BSA particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEONLA-BSA changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.  相似文献   

10.
Liu D  Wu W  Chen X  Wen S  Zhang X  Ding Q  Teng G  Gu N 《Nanoscale》2012,4(7):2306-2310
A strategy for conjugating an antitumor agent to superparamagnetic iron oxide nanoparticles (SPIONs) via a biocleavable ester binding is reported. Paclitaxel (PTX) was selected as a model drug. Both the in vitro and in vivo performance of the conjugates of SPION-PTX was investigated respectively. PTX can be released slowly through the hydrolysis of the ester bond in a pH-dependent manner and the SPION-PTX has near equal cytotoxity to the clinical PTX injection (Taxol) at the equivalent dose of PTX. Furthermore, the SPION-PTX can accumulate in tumor tissues as demonstrated by MRI and exhibit better tumor suppression effect than Taxol in vivo. The above good performance of the SPION-PTX together with the good biocompatibility of the SPIONs would promote greatly the application of the SPIONs in the biomedicine field.  相似文献   

11.
《Ceramics International》2023,49(12):20118-20126
When nanomaterials with antibacterial properties were sent to the infected area, it was predicted that infection and related complications could be prevented. The nanoparticles can be designed to possess magnetic and luminescence (magneto-luminescent) properties to be effectively targeted and localized at the infection foci without dispersing into the body. Simultaneously, the magneto-luminescent characteristic of particles allows visualization and confirmation of localized particles at the desired area. In this regard, there are no studies on the use of antibacterial magneto-luminescent bioactive glass for orthopedic applications and the treatment of orthopedic device-related infections. In this study, antibacterial magneto-luminescent 58S bioactive glasses were synthesized by the modified Stöber using coupled with a layer-by-layer assembly approach to possess core/shell particle morphology. SPION/Bioactive glass nanoparticles had an average size of 50 nm and displayed superparamagnetic behavior. While the saturation magnetization value (σs) of the undoped 58S sample was 25.32 emu/g, that of the co-doped sample (2% Eu, 2% Zn) was 21.74 emu/g; this showed that the doping slightly reduced the magnetization value. Europium (Eu) doping of SPION/Bioactive glass nanoparticles induced characteristic red emission originating from Eu emissions belonging to 5D07FJ (J = 1–4) transitions and the strongest peak was at 612 nm (electric-dipole transition, 5D07F2). Color chromaticity coordinates confirmed emission in the red region. XPS spectrum revealed the existence of Eu and Zn dopant elements in 58S bioactive glass. After soaking characteristic peaks at 31.74° and 45.43° belonging to the hexagonal hydroxyapatite phase were detected in the XRD data, confirming the SEM images. 2% Eu doped SPION/Bioactive glass nanoparticles had the highest osteoblast viability up to 7 days in vitro, while doping the samples with 2% zinc did not yield bone cell viability as high as the Eu doped ones. Importantly, Eu doped SPION/Bioactive glass nanoparticles inhibited gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) growth up to 48 h in vitro. The results showed that Eu doping of SPION/Bioactive glass nanoparticles increased osteoblast viability and inhibited bacterial growth, while possessing superparamagnetic properties and exhibiting red luminescence.  相似文献   

12.
It is important to understand the nanomaterials intracellular trafficking and distribution and investigate their targeting into the nuclear area in the living cells. In our previous study, we firstly observed penetration of nonmodified positively charged carbon dots decorated with quaternary ammonium groups (QCDs) into the nucleus of mouse NIH/3T3 fibroblasts. Thus, in this work, we focused on deeper study of QCDs distribution inside two healthy mouse NIH/3T3 and L929 cell lines by fluorescence microspectroscopy and performed a comprehensive cytotoxic and DNA damage measurements. Real-time penetration of QCDs across the plasma cell membrane was recorded, concentration dependent uptake was determined and endocytic pathways were characterized. We found out that the QCDs concentration of 200 µg/mL is close to saturation and subsequently, NIH/3T3 had a different cell cycle profile, however, no significant changes in viability (not even in the case with QCDs in the nuclei) and DNA damage. In the case of L929, the presence of QCDs in the nucleus evoked a cellular death. Intranuclear environment of NIH/3T3 cells affected fluorescent properties of QCDs and evoked fluorescence blue shifts. Studying the intracellular interactions with CDs is essential for development of future applications such as DNA sensing, because CDs as DNA probes have not yet been developed.  相似文献   

13.
A new procedure for the synthesis of Prussian Green, using HNO3 or dioxane media, is proposed. Synthesis from aqueous H3Fe(CN)6 is described. I.R. spectra of solids and of colloidal suspensions of Prussian Brown, Prussian Green and Prussian Blue are recorded and discussed. An explanation for the 1960 cm?1 vibration stretching is proposed. The identity between Prussian and Turnbull Blue is questioned owing to I.R. results. A mechanism is proposed for the suggested oxyreduction reaction, based on analytical and mass spectroscopy data. Protonation of the complexed iron plays an important role in these reactions. Explanations for contradictory properties and Mössbauer results cited in literature are given.  相似文献   

14.
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.  相似文献   

15.
Superparamagnetic iron oxide nanoparticles (SPION) have emerged as an MRI contrast agent for tumor imaging due to their efficacy and safety. Their utility has been proven in clinical applications with a series of marketed SPION-based contrast agents. Extensive research has been performed to study various strategies that could improve SPION by tailoring the surface chemistry and by applying additional therapeutic functionality. Research into the dual-modal contrast uses of SPION has developed because these applications can save time and effort by reducing the number of imaging sessions. In addition to multimodal strategies, efforts have been made to develop multifunctional nanoparticles that carry both diagnostic and therapeutic cargos specifically for cancer. This review provides an overview of recent advances in multimodality imaging agents and focuses on iron oxide based nanoparticles and their theranostic applications for cancer. Furthermore, we discuss the physiochemical properties and compare different synthesis methods of SPION for the development of multimodal contrast agents.  相似文献   

16.
Superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs) were synthesized by co-precipitation using polyvinyl alcohol (PVA) as a capping agent under alkaline condition. The produced X-ray diffraction (XRD) pattern evidenced the presence of peaks corresponding to the inverse spinel structure of the prepared SPIONs. Debye-Scherrer and field emission scanning microscopy (FESEM) showed the prepared SPIONs to be well-defined with about <?50?nm size. Likewise, the superparamagnetic properties of the SPIONs measured by Vibrating Sample Magnetometer (VSM) showed high saturation magnetization (~ 65.36?emu/g). The in vitro cytotoxicity studies on Neuro2A and HUVEC cells have mentioned low toxic and non-toxic SPIONs, respectively in a range of concentrations (1.17–150?μg/ml), thus, we reckon that the synthesized SPIONs will have persistent utilization in different fields of medical applications.  相似文献   

17.
Magnetic nanoparticles that are currently explored for various biomedical applications exhibit a high propensity to minimize total surface energy through aggregation. This study introduces a unique, thermoresponsive nanocomposite design demonstrating substantial colloidal stability of superparamagnetic Fe3O4 nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating was accomplished in different buffer systems, pH 7.4, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and l-α-dipalmitoylphosphatidyl glycerol (DPPG). Particle size and zeta potential were measured by dynamic laser light scattering. Heating behavior within an alternating magnetic field was compared between the commercial MFG-1000 magnetic field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product quality of lipid-coated SPIONs was significantly dependent on the colloidal stability of uncoated SPIONs during the coating process. Greatest stability was achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 ± 1.7 nm; zeta potential = -47.1 ± 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG layer effectively reduced the impact of buffer components on particle aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 ± 13.9 nm; zeta potential = -19.1 ± 2.3 mV). The configuration of the magnetic field generator significantly affected the heating properties of fabricated SPIONs. Heating rates of uncoated nanoparticles were substantially dependent on buffer composition but less influenced by particle concentration. In contrast, thermal behavior of lipid-coated nanoparticles within an alternating magnetic field was less influenced by suspension vehicle but dramatically more sensitive to particle concentration. These results underline the advantages of lipid-coated SPIONs on colloidal stability without compromising magnetically induced hyperthermia properties. Since phospholipids are biocompatible, these unique lipid-coated Fe3O4 nanoparticles offer exciting opportunities as thermoresponsive drug delivery carriers for targeted, stimulus-induced therapeutic interventions.

PACS

7550Mw; 7575Cd; 8185Qr  相似文献   

18.
A pH-responsive polymer derived from polyethyleneimine with zwitterionic function was used as a shell around super paramagnetic iron oxide nanoparticles (SPIONs), to introduce an efficient drug carrier for cancer drug delivery and imaging. Core–shell magnetic Fe3O4@FA-PEI-SUC (SUC: Succinate conjugated) nanoparticles were attained and characterized. Right chemical attachments, 61.34% modification of primary amino groups of poly(ethyleneimine) (PEI) in PEI–SUC, spherical shape, core–shell structure, crystal structure of SPIONs, 18.23% polymer coating of NPs, 8% decrease in magnetization following polymer coating around SPIONs, doxorubicin loading efficiency 85.19%, two times more released amount in acidic pH, and proper toxicity results were obtained by different analysis methods.  相似文献   

19.
We report in vitro and in vivo magnetic resonance (MR) imaging of C6 glioma cells with a novel acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (Fe3O4 NPs). In the present study, APTS-coated Fe3O4 NPs were formed via a one-step hydrothermal approach and then chemically modified with acetic anhydride to generate surface charge-neutralized NPs. Prussian blue staining and transmission electron microscopy (TEM) data showed that acetylated APTS-coated Fe3O4 NPs can be taken up by cells. Combined morphological observation, cell viability, and flow cytometric analysis of the cell cycle indicated that the acetylated APTS-coated Fe3O4 NPs did not significantly affect cell morphology, viability, or cell cycle, indicating their good biocompatibility. Finally, the acetylated APTS-coated Fe3O4 nanoparticles were used in magnetic resonance imaging of C6 glioma. Our results showed that the developed acetylated APTS-coated Fe3O4 NPs can be used as an effective labeling agent to detect C6 glioma cells in vitro and in vivo for MR imaging. The results from the present study indicate that the developed acetylated APTS-coated Fe3O4 NPs have a potential application in MR imaging.  相似文献   

20.
Multifunctional silica colloidal composites with enhanced photoluminescence (PL) and superparamagnetism are reported. Enhanced PL and superparamagnetism were achieved by encapsulating a mixture layer of quantum dots (QDs) and superparamagnetic iron oxide nanoparticles (SPIONs) within a silica sphere, wherein QDs and SPIONs were capped by 3-mercaptopropionic acid (MPA) and 2-carboxy ethyl phosphonic acid (CEPA), respectively. The silica composites encapsulating a mixture layer of QDs and SPIONs, i.e., S(Q,M)S core(layer)shell architectures with various diameters (80, 360, and 900 nm) were successfully prepared by utilizing electrostatic interaction between positively charged amine-functionalized silica (S) and negatively charged mixture of QD–MPA (Q) and SPION–CEPA (M) and then, by forming a silica shell of 10–20 nm. The S(Q,M)S showed more than twice higher PL intensity than MPA-capped QD with the same QD concentration. Increasing the molar ratio of M/Q from 0.02 to 0.05 in the S(Q,M)S increased the saturation magnetization value from 0.15 to 0.62 emu/g. The S(Q,M)S composites with enhanced PL intensity and superparamagnetism are expected to be a plausible probe material for bioimaing and sensing application. Also, the current synthetic strategy for S(Q,M)S composites is expected to be extendible to include other functional nanoparticles.  相似文献   

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