Sized Iron Oxide Nanoparticles Research Articles

Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile

BackgroundIron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments.ResultsThe optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM− 1s− 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg.ConclusionsThis study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.

Magnetic bioactive glass nano-heterostructures: a deeper insight into magnetic hyperthermia properties in the scope of bone cancer treatment.

Primary bone cancers commonly involve surgery to remove the malignant tumor, complemented with a postoperative treatment to prevent cancer resurgence. Studies on magnetic hyperthermia, used as a single treatment or in synergy with chemo- or radiotherapy, have shown remarkable success in the past few decades. Multifunctional biomaterials with bone healing ability coupled with hyperthermia property could thus be of great interest to repair critical bone defects resulting from tumor resection. For this purpose, we designed superparamagnetic and bioactive nanoparticles (NPs) based on iron oxide cores (γ-Fe2O3) encapsulated in a bioactive glass (SiO2-CaO) shell. Nanometric heterostructures (122 ± 12 nm) were obtained through a two-step process: co-precipitation of 16 nm sized iron oxide NPs, followed by the growth of a bioactive glass shell via a modified Stöber method. Their bioactivity was confirmed by hydroxyapatite growth in simulated body fluid, and cytotoxicity assays showed they induced no significant death of human mesenchymal stem cells after 7 days. Calorimetric measurements were carried out under a wide range of alternating magnetic field amplitudes and frequencies, considering clinically relevant parameters, and some were made in viscous medium (agar) to mimic the implantation conditions. The experimental specific loss power was predictable with respect to the Linear Response Theory, and showed a maximal value of 767 ± 77 W gFe-1 (769 kHz, 23.9 kA m-1 in water). An interesting value of 166 ± 24 W gFe-1 was obtained under clinically relevant conditions (157 kHz, 23.9 kA m-1) for the heterostructures immobilized in agar. The good biocompatibility, bioactivity and heating ability suggest that these γ-Fe2O3@SiO2-CaO NPs are a promising biomaterial to be used as it is or included in a scaffold to heal bone defects resulting from bone tumor resection.

Recent advances in iron oxide nano-materials fortumor treatment

The fundamental research on iron oxide nano-materials has been going on for a whole century, people are increasingly feeling the huge potential value of iron oxide nano-materials in medical area. Up to now, iron oxide nanomaterial still is the only one inorganic nanoparticles which have been approved by Food and Drug Administration of America (FDA) for clinical drug application, and have been played a great role in MRI medical or iron-supplementary medicine. Recently, with the development of chemistry technology, the application of chemical modification strategy become important for regulating the iron oxide nanoparticles of size, morphology, elements and surface functionalization, making the properties better and improving biocompatibility of iron oxide nano-materials widely used in medicine field, and especially in the tumor treatment. Interestingly, the biological effects of iron oxide nano-materials are closely relevant to their chemical composition, morphology, and surface performance, such as the well-known magnetothermal effect and enzyme effect. The synthesis method of iron oxide nano-materials is the key factor to its special chemical properties, and many available approaches have been developed. For example, thermal decomposition has been realized as an outstanding method and can obtain iron oxide nanocrystals with better morphology. However, coprecipitation method is more suitable for the clinic use. Here, the synthesis methods of iron oxide nanomaterials and the medical applications for tumor treatment will be discussed in details. The iron oxide nano-materilas own functional value has been constantly exploring and expanding from the application of contrast agent and iron supplement in the past to the wide study of enzyme activity, the recent functional drug design and immune activation. For the future development of iron oxide materilas, it not only need to meet the basic requirements of biomedical materials, but also overcome the challenges in the complex pathological environment of tumors. Different tumor types have different pathological characteristics, and the level of heterogeneity and malignancy will affect the therapeutic effect of iron oxide nanoparticles. Firstly, we could investigate the synthesis of medical magnetic nanomaterials with high performance and expand their clinical applicability to solve the biological problems of tumors and make them more specific and targeted. A new generation of intelligent tumor drugs preparation based on iron oxide nanoparticles with traditional clinical biomaterials should be explored deeply. Lastly, novel characterization techniques and strategies for construction and modification should be developed. We believed the iron oxide nano-materials will hold a great promise in improving national health.

Elaboration of Superparamagnetic and Bioactive Multicore–Shell Nanoparticles (γ-Fe2O3@SiO2-CaO): A Promising Material for Bone Cancer Treatment

The past few decades have seen the development of new bone cancer therapies, triggered by the discovery of new biomaterials. When the tumoral area is small and accessible, the common clinical treatment implies the tumor mass removal followed by bone reconstruction or consolidation with a bioceramic or a metallic scaffold. Even though the treatment also involves chemotherapy or radiotherapy, resurgence of cancer cells remains possible. We have thus designed a new kind of heterostructured nanobiomaterial, composed of SiO2-CaO bioactive glass as the shell and superparamagnetic γ-Fe2O3 iron oxide as the core in order to combine the benefits of bone repair thanks to the glass bioactivity and cancer cell destruction through magnetic hyperthermia. These multifunctional core-shell nanoparticles (NPs) have been obtained using a two-stage procedure, involving the coprecipitation of 11 nm sized iron oxide NPs followed by their encapsulation inside a bioactive glass shell by sol-gel chemistry. The as-produced spherical multicore-shell NPs show a narrow size distribution of 73 ± 7 nm. Magnetothermal loss measurements by calorimetry under an alternating magnetic field and in vitro bioactivity assessment performed in simulated body fluid showed that these heterostructures exhibit a good heating capacity and a fast mineralization process (hydroxyapatite forming ability). In addition, their in vitro cytocompatibility, evaluated in the presence of human mesenchymal stem cells during 3 and 7 days, has been demonstrated. These first findings suggest that γ-Fe2O3@SiO2-CaO heterostructures are a promising biomaterial to fill bone defects resulting from bone tumor resection, as they have the ability to both repair bone tissue and act as thermoseeds for cancer therapy.

From wustite to hematite: thermal transformation of differently sized iron oxide nanoparticles in air

We have investigated the oxidation behavior of iron oxide nanoparticles in air at elevated temperatures. By wet chemical synthesis under reducing conditions, polycrystalline iron oxide nanoparticles of different sizes were produced. The samples were characterized by x-ray diffraction and transmission electron microscopy. The freshly prepared particles show dominantly the wustite phase and, in addition, one or both of the spinel-like phases maghemite or magnetite. The hematite phase is absent. By annealing under air at different temperatures, we observe a successive transformation of the initial phases to phases of higher oxidation state, until the samples consist completely of the hematite phase. During this transformation, the relative amount and the evolution of the crystallite sizes of the different phases are in the focus of the investigation. We found that the maximum temperature required for a full conversion into the hematite phase depends on the particle size and increases for the larger particles. At the same time, the average crystallite size of the large particles decreases during the initial annealing procedure, passing through a minimum, before increasing again until single crystalline particles are formed.

Uniformly sized iron oxide nanoparticles for efficient gene delivery to mesenchymal stem cells

Recent advances in nanomaterials have made iron oxide nanoparticles (IONPs) as an innovative approach for the delivery of genes. However, the effectiveness of IONPs-assisted gene delivery is currently suffering from their poor uniformity, which not only exhibits detrimental effect on the magnetic property, but also leads to the poor reproducibility to maintain the optimal gene delivery. To this end, the present study developed extremely uniform 15 nm-sized IONPs with a good monodispersity in water phase. These ultra-uniform IONPs exhibit notable potentials for an efficient gene delivery to human mesenchymal stem cells (hMSCs) with the assistance of magnetic force, which partly owes to their abilities to facilitate the cellular uptake, as well as to induce the rapid DNA release and the following nuclear transport. Besides, no significant detrimental effects of these IONPs are observed either on the proliferation or the multi-lineage differentiation potential of hMSCs. The current study highlights the potential advantages of designing extremely uniform magnetic nanomaterials for an efficient and safe delivery of genes to stem cells.

Apple pectin supported superparamagnetic (γ-Fe2O3) maghemite nanoparticles with antimicrobial potency

Magnetic nanoparticles are themselves a fascinating world due to their various applications in different fields mainly biomedical, catalysis, storage devices and many more. Till now magnetites have been explored extensively through different routes whereas another oxide of iron that is maghemite needs attention and yet to be discovered in different aspects. Here we show the simple, facile and less time consuming method to synthesize superparamagnetic maghemite nanoparticles. The highlights and novelty of the synthesis are marked by the use of sodium borohydride to obtain small sized iron oxide nanoparticles starting from a transition metal complex and further stabilizing them with a polysaccharide that is apple pectin. The maghemite nanoparticles thus synthesized, are characterized by SEM, TEM and XRD whereas, pectin binding with nanoparticles is confirmed by FTIR. The size of nanoparticles obtained is between 2 and 6 nm. The phase clarity of maghemites has been derived using Mossbauer spectra. Along with this, their antimicrobial behavior has also been studied using four different bacterial strains P. aerugenosa, S. aureus B. cereus and S. typhii. The nanoparticles were found to inhibit the growth of bacteria. The present work proposes green synthesis of maghemite nanoparticles in water as solvent and supports waste management by using polysaccharide obtained from apple peel.

Novel method for rapid toxicity screening of magnetic nanoparticles

Iron oxide nanoparticles have attracted a great deal of research interest and have been widely used in bioscience and clinical research including as contrast agents for magnetic resonance imaging, hyperthermia and magnetic field assisted radionuclide therapy. It is therefore important to develop methods, which can provide high-throughput screening of biological responses that can predict toxicity. The use of nanoelectrodes for single cell analysis can play a vital role in this process by providing relatively fast, comprehensive, and cost-effective assessment of cellular responses. We have developed a new method for in vitro study of the toxicity of magnetic nanoparticles (NP) based on the measurement of intracellular reactive oxygen species (ROS) by a novel nanoelectrode. Previous studies have suggested that ROS generation is frequently observed with NP toxicity. We have developed a stable probe for measuring intracellular ROS using platinized carbon nanoelectrodes with a cavity on the tip integrated into a micromanipulator on an upright microscope. Our results show a significant difference for intracellular levels of ROS measured in HEK293 and LNCaP cancer cells before and after exposure to 10 nm size iron oxide NP. These results are markedly different from ROS measured after cell incubation with the same concentration of NP using standard methods where no differences have been detected. In summary we have developed a label-free method for assessing nanoparticle toxicity using the rapid (less than 30 minutes) measurement of ROS with a novel nanoelectrode.

Magnetic nanofluid based non-enzymatic sensor for urea detection

We demonstrate a simple, inexpensive and non-enzymatic optical probe for the detection of urea using functionalized magnetic nanofluid. The nanofluid used here is an oil-in-water magnetic nanoemulsion containing superparamagnetic iron oxide nanoparticles of size ∼10nm. Under a constant magnetic field (∼90G), the magnetic emulsion, forms a one dimensional Bragg diffraction grating with a fixed interparticle spacing. In the presence of urea, the probe showed a large wavelength shift in the visible wavelength range of 880–600nm, due to complexation of urea with the functional moieties that dramatically changes the electrostatic repulsion between emulsion droplets or conformation of adsorbed polymer. The functional moieties, sodium dodecyl sulphate, poly acrylic acid and poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) copolymer are found to be suitable for the measurement of urea in the concentrations range 0.003–0.6, 0.18–33.3 and 2.4–334g/L, respectively. PAA stabilized emulsion is found to be suitable for the selective detection of urea in the presence of biologically important cations such as Na+ and Ca2+. The fast response time of the sensor (less than a second) and the wide urea detection capability are the unique features of the new sensor.

Abstract POSTER-THER-1436: Image-guided and targeted therapy of advanced ovarian cancer using theranostic nanoparticles

Abstract About 80% of ovarian cancer patients are diagnosed at the advanced stage due to lack of a specific symptom for early detection. The major clinical challenges in the treatment of advanced ovarian cancer are inability of complete removal of peritoneal tumor metastases by debulking surgery, and drug resistant recurrent tumors developed in the majority of the patients. To address those clinical challenges, we have developed HER2/neu targeted magnetic iron oxide nanoparticles (IONPs) that efficiently deliver therapeutic and imaging agents into HER2 expressing ovarian cancer cells. Amphiphilic polymer coated 10 nm core size IONPs, without or with PEG modification, were conjugated with near infrared dye (NIR-830) labeled HER2 affibody or HER2 affitoxin, which is a fusing protein containing a HER2 affibody for targeting and a modified PE38 toxin as a therapeutic agent. A chemotherapy drug cisplatin, commonly used for ovarian cancer therapy, was further conjugated to carboxyl groups on the polymer coating of IONP via a coordinate bond. First, we demonstrated targeted drug delivery, and specificity and sensitivity of non-invasive tumor imaging by optical and MR imaging following intravenous (i.v.) or intraperitoneal (i.p.) delivery of the targeted theranostic IONPs in an orthotopic SKOV3 human ovarian cancer xenograft model with a high level of HER2/neu expression. Significant inhibition of the growth of primary ovarian tumor, and peritoneal and lung metastases was found after i.v. or i.p. delivery of cisplatin using 0.5 to 5 mg/Kg of cisplatin equivalent doses of HER2 affibody- or HER2 affitoxin-IONP in the tumor bearing mice once every 5 days for five injections. Furthermore, i.p. delivery of HER2 targeted theranostic IONP-cisplatin showed significantly better responses compared with i.v. delivery of the same nanoparticles. HER2 affitoxin-IONP-cisplatin treated mouse group showed enhanced anti-tumor effect compared to HER affibody-IONP-cisplatin treated mouse group. For both delivery approaches, we detected stronger tumor growth inhibitory effect on peritoneal metastatic tumors compared to the response in the primary ovarian tumors. Interestingly, we observed marked differences in the response to HER2 targeted therapy in different tumor bearing mice in the same group, and in different tumors in the same mouse. We also found that non-invasive optical imaging and MRI can be used to monitor IONP-drug delivery into tumors and to detect good responder or poor responder tumors during the treatment. Therefore, the HER2 targeted and image-guided treatment approach using theranostic IONPs has the potential for further development of a new biomarker targeted therapy for significantly improving survival of the ovarian cancer patients Citation Format: Lily Yang, Minati Satpathy, Liya Wang, Rafal Zielinski, Weiping Qian, Malgorzata Lipowska, Jacek Capala, Andrew Wang, Hui Mao. Image-guided and targeted therapy of advanced ovarian cancer using theranostic nanoparticles [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1436.

Chemical synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications.

Magnetic iron oxide nanoparticles have been extensively investigated for their various biomedical applications including diagnostic imaging, biological sensing, drug, cell, and gene delivery, and cell tracking. Recent advances in the designed synthesis and assembly of uniformly sized iron oxide nanoparticles have brought innovation in the field of nanomedicine. This Account provides a review on the recent progresses in the controlled synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. In particular, it focuses on three topics: stringent control of particle size during synthesis via the "heat-up" process, surface modification for the high stability and biocompatibility of the nanoparticles for diagnostic purposes, and assembly of the nanoparticles within polymers or mesoporous silica matrices for theranostic applications. Using extremely small 3 nm sized iron oxide nanoparticles (ESION), a new nontoxic T1 MRI contrast agent was realized for high-resolution MRI of blood vessels down to 0.2 mm. Ferrimagnetic iron oxide nanoparticles (FION) that are larger than 20 nm exhibit extremely large magnetization and coercivity values. The cells labeled with FIONs showed very high T2 contrast effect so that even a single cell can be readily imaged. Designed assembly of iron oxide nanoparticles with mesoporous silica and polymers was conducted to fabricate multifunctional nanoparticles for theranostic applications. Mesoporous silica nanoparticles are excellent scaffolds for iron oxide nanoparticles, providing magnetic resonance and fluorescence imaging modalities as well as the functionality of the drug delivery vehicle. Polymeric ligands could be designed to respond to various biological stimuli such as pH, temperature, and enzymatic activity. For example, we fabricated tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands. They were utilized to visualize small tumors (<3 mm) via pH-responsive T1 MRI and fluorescence imaging. Also, superior photodynamic therapeutic efficacy in highly drug-resistant heterogeneous tumors was observed. We expect that these multifunctional and bioresponsive nanoplatforms based on uniformly sized iron oxide nanoparticles will provide more unique theranostic approaches in clinical uses.

Water-dispersible ascorbic-acid-coated magnetite nanoparticles for contrast enhancement in MRI

Superparamagnetic iron oxide nanoparticles of size ~5 nm surface functionalized with ascorbic acid (vitamin C) form a stable dispersion in water with a hydrodynamic size of ~30 nm. The anti-oxidant property of ascorbic acid is retained after capping, as evidenced from the capability of converting methylene blue to its reduced leuco form. NMR relaxivity studies show that the ascorbic-acid-coated superparamagnetic iron oxide aqueous nanofluid is suitable as a contrast enhancement agent for MRI applications, coupled with the excellent biocompatibility and medicinal values of ascorbic acid.

Electroactive Prussian Blue Encapsulated Iron Oxide Nanostructures for Mediator‐Free Cholesterol Estimation

AbstractIron oxide nanoparticles of size ∼10 nm have been encapsulated into four nanometer thick shells of Prussian blue and were then electrophoretically deposited onto an indium tin oxide substrate. The immobilization of cholesterol oxidase has been done onto the nanostructured film to investigate the kinetic parameters and biosensing characteristics. The fabricated bioelectrode exhibits an electron transfer coefficient and a charge transfer rate constant of 0.45 and 45.15 s−1, respectively. Direct electron transfer properties of the nanostructured film result in 3rd generation cholesterol biosensor. The bioelectrode exhibits high sensitivity (2.15 mAM−1 cm−2), a low Kmapp value (0.07 mM), good stability and high selectivity towards cholesterol.

Granular Fe3 − xO4-CoO hetero-nanostructures produced by in situ seed mediated growth in polyol: magnetic properties and chemical stability

We report here the synthesis of granular composites based on intimately mixed ferrimagnetic Fe3 − xO4 and antiferromagnetic CoO nanocrystals using forced hydrolysis in a polyol solvent. Typically, 10 nm sized iron oxide nanoparticles were pre-formed in diethyleneglycol and used as seeds to grow epitaxially cobalt monoxide nanocrystals, in the same reaction mixture. X-ray diffraction, transmission electron microscopy, 57Fe Mössbauer spectrometry and dc-magnetometry confirmed the production of the desired hetero-nanostructures, of great interest in the field of magnetic recording, and evidenced the formation of a kind of cobalt ferrite solid solution between the initially formed Fe3 − xO4 and latterly deposited CoO nanocrystals. The resulting Co and Fe concentration gradient significantly affects the low temperature magnetization reversal of the composite nanostructures compared to the pristine iron oxide magnetite-like powder. Moreover, with time, air exposure leads to an almost total transformation of the CoO phase into Co3O4 and the electronic displacement of a great part of the Fe2+ ions into Fe3+ ones in the whole grain volume, along with noteworthy low temperature magnetization and coercivity decrease. This material evolution makes the studied composites less valuable for most of the magnetic based functional applications and underlines the importance to pay attention to their storage and integration into functional devices before use.

Simple Solvent-Free Synthesis of Iron-Oxide/Graphene Nanocomposite As Anode Material in Li-Ion Secondary Batteries

Herein, we show a simple solvent-free synthesis of a nanostructured material, composed of uniform sized iron oxide nanoparticles and graphene, for high performance Li-ion secondary battery. The iron-oxide/graphene nanocomposite was directly obtained by heat treatment of a mixture of iron-oleate and graphene. The experimental results showed that uniform sized γ-Fe2O3 nanoparticles were homogeneously embedded in the graphene layers, and they acted as mutual spacers in the nanocomposite to prevent the restacking of the graphene layers and the nanoparticle’s aggregation. As anode material in Li-ion battery, the iron-oxide/graphene nanocomposite exhibits outstanding electrochemical performance due to the synergetic effects of the monodisperse iron oxide nanoparticles and well dispersed graphene. The synthetic procedure is easy to scale up and expected to be extended to prepare other hybrid nanocomposite materials.

Size-controlled self-assembly of superparamagnetic polymersomes.

We report the size-controlled self-assembly of polymersomes through the cooperative self-assembly of nanoparticles and amphiphilic polymers. Polymersomes densely packed with magnetic nanoparticles in the polymersome membrane (magneto-polymersome) were fabricated with a series of different sized iron oxide nanoparticles. The distribution of nanoparticles in a polymersome membrane was size-dependent; while small nanoparticles were dispersed in a polymer bilayer, large particles formed a well-ordered superstructure at the interface between the inner and outer layer of a bilayer membrane. The yield of magneto-polymersomes increased with increasing the diameter of incorporated nanoparticles. Moreover, the size of the polymersomes was effectively controlled by varying the size of incorporated nanoparticles. This size-dependent self-assembly was attributed to the polymer chain entropy effect and the size-dependent localization of nanoparticles in polymersome bilayers. The transverse relaxation rates (r2) of magneto-polymersomes increased with increasing the nanoparticle diameter and decreasing the size of polymersomes, reaching 555 ± 24 s(-1) mM(-1) for 241 ± 16 nm polymersomes, which is the highest value reported to date for superparamagnetic iron oxide nanoparticles.

Abstract 2671: Multimodality imaging of ovarian cancer using HER2 affibody conjugated nanoparticles.

Abstract Objectives: Specific and sensitive detection of ovarian cancer using non-invasive or intraoperative imaging approaches holds great promise for improving survival of the cancer patients through early diagnosis of ovarian cancer and image-guided surgery. In this study, we have developed Near infrared (NIR) dye labeled HER2 targeted magnetic iron oxide nanoparticles (IONPs) that enable detecting orthotopic ovarian cancers in nude mice using five imaging approaches, including 2D optical imaging, 3D-fluorescence tomography, MRI, spectroscopic imaging, and photoacoustic imaging.Methods: HER2 affibodies (ZHER2:342) were labeled with a NIR-dye 830 and then conjugated to a 10 nm core size IONP coated with amphiphilic polymer. Sensitivity of different imaging approaches in cancer detection was determined by direct injection of 5 x 103 to 3 x 106 of the nanoparticle probe-labeled tumor cells into the ovary of the mice and then imaged using 2D Kodak in vivo optical imaging system, MRI, and three new intraoperative hand-held imaging devices, including Spectroscopic, 3D-fluorescent tomography and photoacoustic imaging. Specificity of targeted tumor imaging was demonstrated by system delivery of the NIR830-ZHER2:342-IONP imaging probes in orthotopic human ovarian cancer xenograft models in nude mice. Histological examination of tumor and normal tissues further confirmed tumor targeting specificity.Results: HER2 affibody conjugated IONPs are excellent imaging probes for 2D-NIR optical, 3D-fluorescence tomography, spectroscopic device, photoacoustic and MR imaging of HER2 positive ovarian cancer lesions. Both 2D-optical imaging and MRI were able to detect ovarian tumors as small as 2 mm in size non-invasively. Photoacoustic imaging showed 5-times higher NIR signal in the tumor bearing mice injected with HER2 targeted IONPs than that of non-targeted IONP injected mice. However our handheld spectroscopic device result illustrated a high sensitivity in detection of small metastatic tumor lesions in the peritoneal cavity intra-operatively . Prussian blue staining revealed the presence of HER2 targeted IONPs in the tumor lesion as well as distant metastases lesions. Similarly all the above imaging systems were sensitive to detect at least 104 tumor cells labeled with HER2 affibody conjugated IONPs and implanted into the ovary for 24h. The ability of multi-modality tumor imaging following systemic delivery of single targeted nanoparticle platform make it possible for taking advantages of different imaging methods to increase sensitivity and specificity of tumor targeting and imaging. Conclusion: Based on the above results, the NIR dye-labeled and HER2 targeted IONPs developed by our group have great potential for development of multimodality imaging approaches that can be applied to ovarian cancer detection, image-guided and targeted therapy, and image-guided surgery. Citation Format: Minati Satpathy, Weiping Qian, Rafal Zielinski, Liya Wang, Lei Xi, Jacek Capala, Andrew Wang, Malgorzata Lipowska, Brad A. Kairdolf, Huabei Jiang, Shuming Nie, Hui Mao, Lily Yang. Multimodality imaging of ovarian cancer using HER2 affibody conjugated nanoparticles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2671. doi:10.1158/1538-7445.AM2013-2671

Iron Oxide Magnetic Nanoparticles: Characterization and Toxicity Evaluation by In Vitro and In Vivo Assays

The aim of this study was to evaluate the biological properties of iron oxide nanoparticles (IO‐NPs) obtained in the aqueous suspension. The iron oxide nanoparticles were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biocompatibility of the iron oxide was demonstrated by the in vitro quantification of HeLa cells viability using propidium iodide (PI) and fluorescein diacetate (FdA) and the MTT colorimetric assay. The toxicity of small size iron oxide nanoparticles was also evaluated by means of histological examination on male Brown Norway rats after intraperitoneal injection. At the tested concentrations, the nanoparticles proved to be not cytotoxic on HeLa cells. The rat’s behavior, as well as the histopathological aspect of liver, kidney, lung, and spleen tissues at 48 h after intraperitoneal injection did not present any modifications. The in vivo and in vitro assays suggested that the IO‐NPs could be further used for developing new in vivo medical applications.

Basics of magnetic nanoparticles for their application in the field of magnetic fluid hyperthermia

The use of non-invasive alternating magnetic field (AMF) on biocompatible, small sized iron oxide nanoparticles can be used for heat generation in magnetic hyperthermia or for contrast enhancement of biological tissue. However, the behavior of magnetic nanoparticle in the presence of magnetic field is restricted by their size, shape, surface defects, and coatings. Hence, it becomes imperative to closely monitor the magnetic properties of the nanoparticles as current novel formulations of nanoparticles being developed for tissue targeting involves conjugating a magnetic nanoparticle with a site specific ligand or a peptide. Thus, in this review article we have reviewed the effect of size, shape, doping, and surface coating on the magnetic properties of the nanoparticle. Finally we have concluded with the clinical status of magnetic nanoparticle in the field of magnetic fluid hyperthermia.

Solvent free fabrication of nanoporous TiO2 filters using organic–inorganic nanocomposites

Abstract Nanoporous TiO 2 filters with 50 nm mean pore size are synthesized by using commercial TiO 2 nanoparticles and polyvinylpyrrolidone with an easy and low cost route that did not involve any solvent. Crystal structure and surface morphologies are studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. X-ray photoelectron microscopy (XPS) is used to confirm the filtering process by analyzing pre- and post-filter affluent containing nanoparticles to simulate the filtration of micrometer (bacteria) and nanometer (virus) species. Greater than 85% filtering efficiency is obtained during the filtering of a mixture of water and 30 nm mean crystallite size iron oxide nanoparticles.