Polymer-coated Iron Oxide Nanoparticles Research Articles

Hybrid hydrogels support neural cell culture development under magnetic actuation at high frequency

The combination of hydrogels and magnetic nanoparticles, scarcely explored to date, offers a wide range of possibilities for innovative therapies. Herein, we have designed hybrid 3D matrices integrating natural polymers, such as collagen, chitosan (CHI) and hyaluronic acid (HA), to provide soft and flexible 3D networks mimicking the extracellular matrix of natural tissues, and iron oxide nanoparticles (IONPs) that deliver localized heat when exposed to an alternating magnetic field (AMF). First, colloidally stable nanoparticles with a hydrodynamic radius of ∼20 nm were synthesized and coated with either CHI (NPCHI) or HA (NPHA). Then, collagen hydrogels were homogeneously loaded with these coated-IONPs resulting in soft (E0 ∼ 2.6 kPa), biodegradable and magnetically responsive matrices. Polymer-coated IONPs in suspension preserved primary neural cell viability and neural differentiation even at the highest dose (0.1 mg Fe/mL), regardless of the coating, even boosting neuronal interconnectivity at lower doses. Magnetic hydrogels maintained high neural cell viability and sustained the formation of highly interconnected and differentiated neuronal networks. Interestingly, those hydrogels loaded with the highest dose of NPHA (0.25 mgFe/mg polymer) significantly impaired non-neuronal differentiation with respect to those with NPCHI. When evaluated under AMF, cell viability slightly diminished in comparison with control hydrogels magnetically stimulated, but not compared to their counterparts without stimulation. Neuronal differentiation under AMF was only affected on collagen hydrogels with the highest dose of NPHA, while non-neuronal differentiation regained control values. Taken together, NPCHI-loaded hydrogels displayed a superior performance, maybe benefited from their higher nanomechanical fluidity. Statement of significanceHydrogels and magnetic nanoparticles are undoubtedly useful biomaterials for biomedical applications. Nonetheless, the combination of both has been scarcely explored to date. In this study, we have designed hybrid 3D matrices integrating both components as promising magnetically responsive platforms for neural therapeutics. The resulting collagen scaffolds were soft (E0 ∼ 2.6 kPa) and biodegradable hydrogels with capacity to respond to external magnetic stimuli. Primary neural cells proved to grow on these substrates, preserving high viability and neuronal differentiation percentages even under the application of a high-frequency alternating magnetic field. Importantly, those hydrogels loaded with chitosan-coated iron oxide nanoparticles displayed a superior performance, likely related to their higher nanomechanical fluidity.

Design and development of a magnetic field-enabled platform for delivering polymer-coated iron oxide nanoparticles to breast cancer cells

The current literature mostly contains relatively vague descriptions of techniques for implementing in vitro magnetic targeting delivery of iron oxide nanoparticles (IONPs), leading to irreproducible processes and incomparable findings. This discrepancy often arises from the varying exposure of IONPs to the non-uniform magnetic field and differences in the concentration of the polymer-coated IONPs. Hence, we meticulously designed and built a system comprising a platform constructed from polyoxymethylene sheets, which securely holds the permanent magnets, and the cell culture plate. We also tailored the preparation process of the IONPs and the in vitro toxicity studies. The inherent characteristics of IONPs are further enhanced by their coating with natural polymers, alginate (Alg) and chitosan (CS).•The design and construction of the platform were carried out using a laser engraving/cutting machine along with graphic design software. The precise locations of the permanent magnets relative to the cell culture plate were determined via a Gaussmeter.•The quantities of the components in the formulation and the method for fabricating the CS/Alg-coated IONPs (CS/Alg-IONPs) were optimized to ensure that the desired physicochemical properties were obtained.•The cultivation and cytotoxicity evaluation of the fabricated CS/Alg-IONPs against MCF-7 breast cancer cells were described.

High-Dose Exposure to Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells.

Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe2O3 and Fe2O3@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe3O4-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 μg/mL. However, when the cells were exposed to higher concentrations (200-400 μg/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells.

Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models

BackgroundThe widespread use of nano-biomaterials (NBMs) has increased the chance of human exposure. Although ingestion is one of the major routes of exposure to NBMs, it is not thoroughly studied to date. NBMs are expected to be dramatically modified following the transit into the oral-gastric-intestinal (OGI) tract. How these transformations affect their interaction with intestinal cells is still poorly understood. NBMs of different chemical nature—lipid-surfactant nanoparticles (LSNPs), carbon nanoparticles (CNPs), surface modified Fe3O4 nanoparticles (FNPs) and hydroxyapatite nanoparticles (HNPs)—were treated in a simulated human digestive system (SHDS) and then characterised. The biological effects of SHDS-treated and untreated NBMs were evaluated on primary (HCoEpiC) and immortalised (Caco-2, HCT116) epithelial intestinal cells and on an intestinal barrier model.ResultsThe application of the in vitro SDHS modified the biocompatibility of NBMs on gastrointestinal cells. The differences between SHDS-treated and untreated NBMs could be attributed to the irreversible modification of the NBMs in the SHDS. Aggregation was detected for all NBMs regardless of their chemical nature, while pH- or enzyme-mediated partial degradation was detected for hydroxyapatite or polymer-coated iron oxide nanoparticles and lipid nanoparticles, respectively. The formation of a bio-corona, which contains proteases, was also demonstrated on all the analysed NBMs. In viability assays, undifferentiated primary cells were more sensitive than immortalised cells to digested NBMs, but neither pristine nor treated NBMs affected the intestinal barrier viability and permeability. SHDS-treated NBMs up-regulated the tight junction genes (claudin 3 and 5, occludin, zonula occludens 1) in intestinal barrier, with different patterns between each NBM, and increase the expression of both pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-22, IL-10). Notably, none of these NBMs showed any significant genotoxic effect.ConclusionsOverall, the results add a piece of evidence on the importance of applying validated in vitro SHDS models for the assessment of NBM intestinal toxicity/biocompatibility. We propose the association of chemical and microscopic characterization, SHDS and in vitro tests on both immortalised and primary cells as a robust screening pipeline useful to monitor the changes in the physico-chemical properties of ingested NBMs and their effects on intestinal cells.

Recent advances in polymer-coated iron oxide nanoparticles as magnetic resonance imaging contrast agents

The surface–chemically modified superparamagnetic iron oxide nanoparticles are broadly investigated as magnetic resonance imaging contrast agents based on their unique characteristics such as high magnetization values, diameter from 4 to 100 nm, and narrow distribution of particle size. However, naked nanoparticles might be easily oxidized by the air leading to loss of dispersibility and magnetization. Therefore, suitable surface coating strategies were developed to increase the stability of magnetic iron oxide contrast agents in the physiological conditions. In addition, the polymer-coated agents possess an improved biocompatibility in comparison with conventional agents. This review discusses important aspects of newly developed magnetic contrast agents such as chemical synthesis strategies, physical parameters, relaxivity parameters, the effect of various coatings, and emerging applications. Disadvantages associated with commercially available gadolinium contrast agents are considered, and the advantages of potential applications of iron oxide alternatives to traditional agents are presented. Finally, perspectives of the future developments, applications, and concerns of the magnetic nanoparticles are also included.

Targeted Imaging of CD206 Expressing Tumor-Associated M2-like Macrophages Using Mannose-Conjugated Antibiofouling Magnetic Iron Oxide Nanoparticles.

Although tumor-associated macrophages (TAMs) have been shown to promote cancer progression, their roles in tumor development and resistance to therapy remain to be fully understood, mainly because of the lack of a good approach to evaluate the dynamic changes of heterogeneous macrophages in their residing microenvironment. Here, we report an approach of using antibiofouling PEG-b-AGE polymer-coated iron oxide nanoparticles (IONPs) for targeted imaging of mannose receptor (CD206)-expressing M2-like TAMs. Antibiofouling polymer coatings block non-specific phagocytosis of IONPs by different cells but enable ligand-mediated CD206+ M2-like macrophage targeting after surface functionalizing with mannose (Man-IONP). Costaining tissue sections of the 4T1 mouse mammary tumors using an anti-CD206 antibody and fluorescent dye (TRITC)-labeled Man-IONP showed 94.7 ± 4.5% colocalization of TRITC-Man-IONPs with the anti-CD206 antibody. At 48 h after intravenous (i.v.) injection of Man-IONPs, magnetic resonance imaging of mice bearing orthotopic 4T1 mammary tumors showed a significantly larger IONP-induced decrease of the transverse relaxation time (T 2) in tumors with 29.4 ± 1.5 ms compared to 12.3 ± 3.6 ms in tumors that received non-targeted IONP probes (P < 0.001). Immunofluorescence-stained tumor tissue sections collected at 6, 18, and 24 h after i.v. administration of the nanoprobes revealed that Man-IONPs specifically targeted CD206+ M2-like macrophages in various tumor areas at all time points, while nonconjugated IONPs were absent in the tumor after 18 h. Thus, antibiofouling Man-IONPs demonstrated the capability of explicitly imaging CD206+ M2-like macrophages in vivo and potentials for investigating the dynamics of macrophages in the tumor microenvironment and delivering therapeutics targeting M2-like TAMs.

Magnetically Triggered Release of Entrapped Bioactive Proteins from Thermally Responsive Polymer-Coated Iron Oxide Nanoparticles for Stem-Cell Proliferation.

Nanoparticles could conceal bioactive proteins during therapeutic delivery, avoiding side effects. Superparamagnetic iron oxide nanoparticles (SPIONs) coated with a temperature-sensitive polymer were tested for protein release. We show that coated SPIONs can entrap test proteins and release them in a temperature-controlled manner in a biological system. Magnetically heating SPIONs triggered protein release at bulk solution temperatures below the polymer transition. The entrapped growth factor Wnt3a was inactive until magnetically triggered release, upon which it could increase mesenchymal stem cell proliferation. Once the polymer transition will be chemically adjusted above body temperature, this system could be used for targeted cell stimulation in model animals and humans.

Magnetic glyconanoparticles for selective lectin separation and purification

A modular platform for the separation and purification of lectins using polymer coated iron oxide nanoparticles is developed.

PEG/Dextran Double Layer Influences Fe Ion Release and Colloidal Stability of Iron Oxide Nanoparticles

Despite preliminary confidence on biosafety of polymer coated iron oxide nanoparticles (SPIONs), toxicity concerns have hampered their clinical translation. SPIONs toxicity is known to be due to catalytic activity of their surface and release of toxic Fe ions originating from the core biodegradation, leading to the generation of reactive oxygen species (ROS). Here, we hypothesized that a double-layer polymeric corona comprising of dextran as an interior, and polyethylene glycol (PEG) as an exterior layer better shields the core SPIONs. We found that ROS generation was cell specific and depended on SPIONs concentration, although it was reduced by sufficient PEG immobilization or 100 µM deferoxamine. 24 h following injection, PEGylated samples showed reduction of biodistribution in liver, heterogenous biodistribution profile in spleen, and no influence on NPs blood retention. Sufficient surface masking or administration of deferoxamine could be beneficial strategies in designing and clinical translation of future biomedical SPIONs.

Synthesis and Characterization of Cationic Polymer Coated Iron Oxide Nanoparticles for Delivery of siRNA and Selective Gene Silencing

Synthesis and Characterization of Cationic Polymer Coated Iron Oxide Nanoparticles for Delivery of siRNA and Selective Gene Silencing

Controlled aggregation and cell uptake of thermoresponsive polyoxazoline-grafted superparamagnetic iron oxide nanoparticles.

Hydrophilic polymer-coated iron oxide nanoparticles are potential materials for a plethora of applications in the biotechnological field. Typical such polymers, e.g. dextran or poly(ethylene glycol), lack the ability to tailor the biological response to an environmental trigger, while common responsive polymers such as poly(N-isopropylacrylamide) or poly(acrylic acid) are not suitable for biomedical applications. We present the synthesis and characterization of superparamagnetic iron oxide nanoparticles with thermoresponsive polyoxazoline brushes grafted at unprecedented density using nitrodopamine anchor chemistry. Reversible aggregation/deaggregation is observed in water and biological medium, confirming control over the colloidal stability. Thermal switching of the solubility could only be achieved by global heating of the sample, while local magnetothermal heating did not produce a sufficiently strong temperature gradient through the brush. Varying the polymer composition allows for tuning of the lower critical solution temperature (LCST) as well as the average nanoparticle cluster size obtained upon heating. The LCST of polyoxazolines and the thermal colloidal stability are shown to be greatly affected by ion concentration, by polymer grafting density and also by the presence of serum protein; this shows that transition temperatures of free polymers in water can be very misleading for the design of polymer-coated nanomaterials for biomedical applications. Finally, the thermoresponsive SPION are shown to be non-cytotoxic and with a low cell uptake scaling with the hydration of the polymer brush, which is tuned by the polymer composition. Thus, we demonstrate that pozylated nanoparticles provide the advantages of PEG- and PNIPAM-grafted nanoparticles, but provide a tunable and more easily functionalizable platform for further development.

Biogenic Fabrication of Iron/Iron Oxide Nanoparticles and Their Application

Enshrined in this review are the biogenic fabrication and applications of coated and uncoated iron and iron oxide nanoparticles. Depending on their magnetic properties, they have been used in the treatment of cancer, drug delivery system, MRI, and catalysis and removal of pesticides from potable water. The polymer-coated iron and iron oxide nanoparticles are made biocompatible, and their slow release makes them more effective and lasting. Their cytotoxicity against microbes under aerobic/anaerobic conditions has also been discussed. The magnetic moment of superparamagnetic iron oxide nanoparticles changes with their interaction with biomolecules as a consequence of which their size decreases. Their biological efficacy has been found to be dependent on the shape, size, and concentration of these nanoparticles.

Abstract 3675: Double receptor targeting multifunctional iron oxide nanoparticles drug delivery system for the treatment and imaging of prostate cancer

Abstract Purpose: As an alternative to the drawbacks of current advanced prostate cancer chemotherapy, we propose a multifunctional double targeting drug delivery system that utilizes the combination of two cancer-targeting peptides: a modified luteinizing hormone releasing hormone (LHRH), the ligand for luteinizing hormone releasing hormone receptor (LHRH-R), and AE105, the ligand for urokinase type plasminogen activation receptor (uPAR). Both ligands are fused to amphiphilic polymer coated iron oxide nanoparticles (IONPs) and loaded with the anticancer drug Paclitaxel (PTX) as the payload. Materials and Methods: Targeted IONPs were characterized by both gel electrophoresis and dynamic light scattering (DLS). PTX was absorbed on the IONPs. Drug loading and release characteristics were conducted by HPLC. The binding specificity and the internalization efficiency of the targeted IONPs were both examined by Prussian blue staining and magnetic resonance imaging (MRI). Cytotoxicity of the targeted IONPs was evaluated by MTT assay. Results: Characterization of targeted IONPs by gel electrophoresis confirmed the successful attachment of the peptides to IONPs. Conjugation of peptides to carboxylic groups of polymer coating on IONPs resulted in an increase in the average hydrodynamic size of targeted IONPs (16.34 nm) as compared to non-targeted IONPs (12.51 nm), as well as a decrease of zeta potential from -70.43 mV to -58.06 mV, respectively. Prussian blue staining demonstrated that both, LHRH and AE105 conjugated IONPs were internalized efficiently by cells of the human prostate cancer cell line, PC3. In vitro MRI results showed that double-targeted IONPs significantly maintained T2 MRI contrast effect and reduction of T2 values upon internalization by PC3 cells. MRI imaging confirmed the preferential binding and accumulation of double-targeted IONPs in PC3 cells when compared to normal prostate epithelial cells (RC77N/E). PTX loaded double-targeted IONPs were stable at physiological pH and efficiently released around pH 4, the optimum pH inside the tumor cells. PTX loaded double-targeted IONPs showed an approximately 2-fold reduction in PC3 cell viability when compared to non-targeted IONPs. In addition, the percentage of cell death resulting from the PTX loaded, double-targeted IONPs was very similar to the percentage of cell death attributed to 100 ng/ml of free PTX, thereby demonstrating that their capability of reducing drug concentration. Conclusions: Our results indicate that we have developed a LHRH-R and uPAR targeted IONPs drug delivery system that potentially provides a MRI tractable delivery of cancer therapeutics such as PTX to prostate cancer cells. Therefore, our optimized double-targeted IONPs drug delivery system has the potential to significantly improve the health outcomes and quality of life for cancer patients as a novel type of targeted nanomedicine therapy. Citation Format: Md Shakir U. Ahmed, Mohamed O. Abdalla, Clayton Yates, Jesse Jaynes, Timothy Turner. Double receptor targeting multifunctional iron oxide nanoparticles drug delivery system for the treatment and imaging of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3675. doi:10.1158/1538-7445.AM2015-3675

Abstract 3681: Facile fabrication of MRI-capable and NIR-resonant core-satellite nanomediators for photothermal therapy

Abstract Although many techniques exist for fabricating near-infrared (NIR)-resonant and magnetic resonance imaging (MRI)-capable nanomediators for photothermal cancer therapy, preparing them in an efficient and scalable process remains a significant challenge. In this report, we develop two facile methods to fabricate both NIR-resonant and MRI-capable nanomediators utilizing well developed polysiloxane-containing polymer-coated iron oxide nanoparticles (IONPs). One of the methods is to attach multiple NIR-resonant nanoparticles onto a thiol-modified IONP core through one-step mixing with gold sulfide nanoparticles (Au2S NPs) to fabricate a core-satellite nanomediator. The other strategy is to covalently attach a NIR organic dye onto intact polysiloxane-containing polymer-coated IONPs through facile mixing with siloxane-modified IR820. The successful decoration with either Au2S NPs or IR820 is demonstrated for the resultant nanomediators by absorption spectra and transmission electron microscopy (TEM) images. It is estimated that 10 Au2S NPs and 2×104 dye molecules (loading capacity: 4.5 mg IR820/mg Fe) are attached onto the polymer-coated IONPs, respectively. The hydrodynamic sizes of these novel multifunctional nanomediators are ∼57.5 nm for IONP-Au2S NP and 28.2 nm for IONP-IR820, which are much smaller than traditional gold nanoshell-based designs. The photothermal efficiency of the IONP-Au2S NP and IONP-IR820 nanocomposite solutions under the irradiation of 885 nm NIR laser light is significantly enhanced compared to IONPs alone. The enhancement in photothermal efficiency by the newly developed nanomediators is also investigated in nude mice bearing SUM-159 tumor xenografts. The biodistribution data measured by inductively coupled plasma optical emission spectrometry (ICP-OES) reveal that ∼1% injection dose (ID) of IONP-Au2S NPs and ∼9% ID of IONP-IR820 accumulate into tumor tissue 24 h post intravenous injection at a dose of 20 mg Fe/Kg mouse body weight. The average tumor surface temperature recorded by an infrared camera is increased by 10.8 ± 1.2 °C for the mice administered with IONP-Au2S NPs and 25.7 ± 3.6 °C for the group injected with IONP-IR820, compared to 4.8 ± 0.5 °C for the PBS-injected control mice after laser irradiation with a power of 0.5 W for 10 min. Furthermore, our data reveal that the fabrication will not compromise the IONP core capability as an MRI contrast agent. Taken together, we demonstrate a facile technique to generate NIR-resonant and MRI-capable nanomediators from a polysiloxane-containing polymer-coated IONP platform. The as-developed dual functional nanomediators hold great promise for translatable MRI-guided photothermal cancer therapy. Citation Format: Hongwei Chen, Xiaoqing Ren, Hayley Paholak, Joseph Burnett, Feng Ni, Duxin Sun. Facile fabrication of MRI-capable and NIR-resonant core-satellite nanomediators for photothermal therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3681. doi:10.1158/1538-7445.AM2015-3681

Design considerations for the synthesis of polymer coated iron oxide nanoparticles for stem cell labelling and tracking using MRI.

Iron oxide nanoparticles (IONPs, sometimes called superparamagnetic iron oxide nanoparticles or SPIONs) have already shown promising results for in vivo cell tracking using magnetic resonance imaging (MRI). To fully exploit the potential of these materials as contrast agents, there is still a need for a greater understanding of how they react to physiological conditions. A key aspect is the specific nature of the surface coating, which can affect important properties of the IONPs such as colloidal stability, toxicity, magnetism and labelling efficiency. Polymers are widely used as coatings for IONPs as they can increase colloidal stability in hydrophilic conditions, as well as protect the iron oxide core from degradation. In this tutorial review, we will examine the design and synthesis approaches currently being employed to produce polymer coated IONPs as cell tracking agents, and what considerations must be made. We will also give some perspective on the challenges and limitations that remain for polymer coated IONPs as MRI contrast agents for stem cell tracking.

A facile and cost-effective method for separation of oil-water mixtures using polymer-coated iron oxide nanoparticles.

Catastrophic oil spills and oil from waste waters such as bilge and fracking waters pose major environmental concerns. The limitations of existing cleanup techniques for benign oil remediation has inspired a recent scientific impetus to develop oil-absorbing smart nanomaterials. Magnetic nanocomposites were here designed to allow easy recovery from various systems. In this study, sorption of reference MC252 oil with easy-to-synthesize and low-cost hydrophilic polyvinylpyrrolidone-coated iron oxide nanoparticles is reported for the first time. The one-step modified polyol synthesis in air directly generates water-soluble nanoparticles. Stable polyvinylpyrrolidone-coatings are known to minimize environmental alterations of nanoparticles from aggregation and other processes. Iron oxide provides effective magnetic actuation, while both PVP and iron oxide have low toxicity. These nanoparticles gave quantitative (near 100%) oil removal under optimized conditions. The facile synthesis and ease of use represents a significant improvement over existing techniques.

Abstract 4480: Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers

Abstract Purpose: As an alternative to the drawbacks of current advanced cancer treatments such as conventional chemotherapy, we propose a multifunctional double targeting drug delivery system that utilizes the combination of cancer-targeting peptides fused to amphiphilic polymer coated iron oxide nanoparticles (IONPs) and loaded with suitable anticancer drugs as the payload. Methods: PC3 human prostate cancer cell line will be used initially to test the efficiency of the proposed drug delivery system. Our target sites of choice are the luteinizing hormone releasing hormone receptor (LHRH-R) and the urokinase-type plasminogen activator receptor (uPAR), and docetaxel was selected as the payload. A modified LHRH (ligand for LHRH-R) and AE105 (ligand for uPAR) were conjugated to polymer coated IONPs according to the manufacturer's protocol. Results: Conjugated IONPs were characterized by gel electrophoresis and Dynamic Light Scattering (DLS). IONPs showed expected narrow size distribution after conjugation with peptide ligand. The average hydrodynamic size of non targeted IONPs (36.84 nm) was increased upon conjugation of double peptide to their surface (44.06 nm). Conjugation of peptides to carboxylic groups of polymer coating on IONPs resulted in a decrease of zeta potential from -70.43 mV to -58.06 mV. Prussian blue staining demonstrated that LHRH and AE105 conjugated IONPs were internalized efficiently by the PC3 cells. The drug loading and release capability of conjugated IONPs will be evaluated by HPLC. In addition the internalization of conjugated IONPs will also be examined utilizing Magnetic Resonance Imaging (MRI), and tumor eradication will be determined by MTT assay. Conclusions: We expect a significant enhancement in the binding efficiency of the LHRH-IONPs-AE105 to the prostate cancer cells, increased efficiency in tumor eradication, and better imaging and monitoring capabilities because IONPs can be visualized by MRI during molecular imaging of the prostate cancer cells. Therefore, we believe the optimization of the proposed system will enhance targeted nanomedicine and significantly improve the health outcomes and quality of life for cancer patients because of the following reasons: 1) its ability to deliver anticancer drugs specifically to cancer cells while sparing the surrounding normal tissues, and 2) the capability of in situ monitoring of the therapeutics. Citation Format: Md Shakir U. Ahmed, Mohamed O. Abdalla, Timothy Turner. Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4480. doi:10.1158/1538-7445.AM2014-4480

Dual-responsive polymer-coated iron oxide nanoparticles for drug delivery and imaging applications.

We reported the synthesis and characterization of dual-responsive poly(N-isopropylacrylamide-acrylamide-chitosan) (PAC)-coated magnetic nanoparticles (MNPs) for controlled and targeted drug delivery and imaging applications. The PAC-MNPs size was about 150nm with 70% iron mass content and excellent superparamagnetic properties. PAC-MNPs loaded with anti-cancer drug doxorubicin showed dual-responsive drug release characteristics with the maximum release of drugs at 40°C (∼78%) than at 37°C (∼33%) and at pH of 6 (∼55%) than at pH of 7.4 (∼28%) after 21 days. Further, the conjugation of prostate cancer-specific R11 peptides increased the uptake of PAC-MNPs by prostate cancer PC3 cells. The dose-dependent cellular uptake of the nanoparticles was also significantly increased with the presence of 1.3T magnetic field. The nanoparticles demonstrated cytocompatibility up to concentrations of 500μg/ml when incubated over a period of 24h with human dermal fibroblasts and normal prostate epithelial cells. Finally, pharmacokinetic studies indicated that doxorubicin-loaded PAC-MNPs caused significant prostate cancer cell death at 40°C than at 37°C, thereby confirming the temperature-dependent drug release kinetics and in vitro therapeutic efficacy. Future evaluation of in vivo therapeutic efficacy of targeted image-guided cancer therapy using R11-PAC-MNPs will reinforce a significant impact of the multifunctional PAC-MNPs on the future drug delivery systems.

Development and Characterization of Thermosensitive Polymer- CoatedIron Oxide Nanoparticles as a Novel Ferrofluid

In this work, we aim to study the development and characterization of thermosensitive polymer-coated iron oxide nanoparticles as a novel ferroFluid (fF) with thermosensitive properties. For this purpose, polymerization was conducted in the presence of various ratios of N-isopropylacrylamide (NIPAAm), acrylamide (AAm) and N-vinylpyrrolidone (NVP) as monomers, and N,N´-azobisisobutyronitrile (AIBN) as an initiator. Particles having average sizes of 8 nm and 8–10 nm were respectively observed for Fe3O4/fF and Fe3O4/polymers. As visualized by transmission electron microscopy (TEM) images, both the coated and uncoated iron oxide nanoparticles were uniform in shape and seem to have been monodispersed. Vibrating sample magnetometry (VSM) measurements of Fe3O4/VTES-fF and Fe3O4/Poly (NIPAAm- AAm NVP) at room temperature showed that they had a superparamagnetic nature with saturation magnetization values of 23.14 emu/g and 4.33 emu/g, respectively. In the thermosensitivity analysis, the lower critical solution temperature (LCST) was around 36-40°C, as determined by UV-Vis absorption spectroscopy. Furthermore, the polymerization of (NIPAAm-AAm-NVP) with the surface modified magnetic ferroFluid was confirmed by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). These aqueous, stable, magnetic nanoparticles coated with temperature-sensitive polymers have attracted great attention because of their various applications in the fields of biotechnology and medicine.

Hemostasis Disorders Caused by Polymer Coated Iron Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are inorganic nanomaterials gaining strong clinical interest due to their increasing number of biological and medical applications. The stabilization of SPIONs in a biocompatible stable suspension (bioferrofluid) is generally achieved by an adequate polymeric coating. As many applications using these materials are intended for clinical use through intravenous injection, it is of outmost importance to evaluate their hemostatic behaviour. The aim of this work is to evaluate the hemocompatibility of selected polymer coated bioferrofluids and of their separated components by observing the effects of the bioferrofluid on: the coagulation process--by measuring the prothrombin time (PT) and activated partial thromboplastin time (aPTT)--, the complete blood count (CBC)--Erythrocytes, Leucocytes, Platelets, Hemoglobin and hematocrit--and the hemolysis. A SPIONs/bioferrofluid model consisting of a magnetic core of iron oxide nanoparticles embedded within poly(4-vinyl pyridine) (P4VP) and all coated with polyethylene glycol (PEG) has been selected. By increasing the concentration of the bioferrofluids an inhibitory effect on the intrinsic pathway of blood coagulation is observed, as indicated by significant increase in aPTT in vitro while PT values stay normal. The effect of the coating components on the inhibition of blood coagulation process shows that PEG has no effect on the process while the P4VP-g-PEG copolymer coating has a strong anticoagulant effect indicating that P4VP is at the origin of such effects. The studied bioferrofluids have no effect on the CBC neither they show in vitro hemolytic effect on blood.