Photonic Hydrogels for Synergistic Visual Bacterial Detection and On-Site Photothermal Disinfection.

Rapid and sensitive diagnostics in the early stage of bacterial infection and immediate treatment play critical roles in the control of infectious diseases. However, it remains challenging to develop integrated systems with both rapid detection of bacterial infection and timely on-demand disinfection ability. Herein, we demonstrate a photonic hydrogel platform integrating visual diagnosis and on-site photothermal disinfection by incorporating Fe3O4@C nanoparticles into a poly(hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAAm) matrix. In vitro experiments demonstrate that such a hydrogel can respond to pH variation caused by bacterial metabolism and generate the corresponding color changes to realize naked-eye observation. Meanwhile, its excellent photothermal conversion ability enables it to effectively kill bacteria by destroying cell membranes under near-infrared irradiation. Moreover, the pigskin infection wound model also verifies the bacterial detection performance and disinfection ability of the hydrogel in vivo. Our strategy demonstrates a new approach for visual diagnosis and treatment of bacterial infections.

Photosensitive Polymeric Janus Micromotor for Enzymatic Activity Protection and Enhanced Substrate Degradation.

Immobilizing enzymes into microcarriers is a strategy to improve their long-term stability and reusability, hindered by (UV) light irradiation. However, in such approaches, enzyme-substrate interaction is mediated by diffusion, often at slow kinetics. In contrast, enzyme-linked self-propelled motors can accelerate this interaction, frequently mediated by the convection mechanism. This work reports on a new photosensitive polymeric Janus micromotor (JM) for UV-light protection of enzymatic activity and efficient degradation of substrates accelerated by the JMs. The JMs were assembled with UV-photosensitive modified chitosan, co-encapsulating fluorescent-labeled proteins and enzymes as models and magnetite and platinum nanoparticles for magnetic and catalytic motion. The JMs absorbed UV light, protecting the enzymatic activity and accelerating the enzyme-substrate degradation by magnetic/catalytic motion. Immobilizing proteins in photosensitive JMs is a promising strategy to improve the enzyme's stability and hasten the kinetics of substrate degradation, thereby enhancing the enzymatic process's efficiency.

Radio frequency plasma assisted surface modification of Fe3O4 nanoparticles using polyaniline/polypyrrole for bioimaging and magnetic hyperthermia applications.

Surface modification of superparamagnetic Fe3O4 nanoparticles using polymers (polyaniline/polypyrrole) was done by radio frequency (r.f.) plasma polymerization technique and characterized by XRD, TEM, TG/DTA and VSM. Surface-passivated Fe3O4 nanoparticles with polymers were having spherical/rod-shaped structures with superparamagnetic properties. Broad visible photoluminescence emission bands were observed at 445 and 580 nm for polyaniline-coated Fe3O4 and at 488 nm for polypyrrole-coated Fe3O4. These samples exhibit good fluorescence emissions with L929 cellular assay and were non-toxic. Magnetic hyperthermia response of Fe3O4 and polymer (polyaniline/polypyrrole)-coated Fe3O4 was evaluated and all the samples exhibit hyperthermia activity in the range of 42-45 °C. Specific loss power (SLP) values of polyaniline and polypyrrole-coated Fe3O4 nanoparticles (5 and 10 mg/ml) exhibit a controlled heat generation with an increase in the magnetic field.

Cellulose nanocrystals reinforced highly stretchable thermal-sensitive hydrogel with ultra-high drug loading.

Hydrogels often have poor mechanical properties which limit their application in load-bearing tissues such as muscle and cartilage. In this work, a near-infrared light-triggered stretchable thermal-sensitive hydrogel with ultra-high drug loading was developed by a combination of natural polymeric nanocrystals, a network of synthetic thermo-responsive polymer, and magnetic Fe3O4 nanoparticles. The hydrogels comprise cellulose nanocrystals (CNCs) decorated with Fe3O4 nanoparticles (Fe3O4/CNCs) dispersed homogeneously in poly(N-isopropylacrylamide) (PNIPAm) networks. The composite hydrogels exhibit an extensibility of 2200%. Drug loading of vancomycin (VCM) reached a high value of 10.18 g g-1 due to the dispersion of Fe3O4/CNCs and the interactions between the CNCs and the PNIPAm network. Importantly, the hydrogels demonstrated a thermo-response triggered by NIR, with the temperature increasing from 26 to 41 °C within 60 s. The hydrogels have high biocompatibility evidenced by cell proliferation tests, illustrating that these hydrogels are promising as dressings for wound closure, and wound healing.

Novel Core-Sheath Cu/Cu2O-ZnO-Fe3O4 Nanocomposites with High-Efficiency Chlorine-Resistant Bacteria Sterilization and Trichloroacetic Acid Degradation Performance.

In order to solve two issues of chlorine-resistant bacteria (CRB) and disinfection byproducts (DBPs) in tap water after the chlorine-containing treatment process, an innovative core-sheath nanostructured Cu/Cu2O-ZnO-Fe3O4 was designed and synthesized. The fabrication mechanism of the materials was then systematically analyzed to determine the component and valence state. The properties of CRB inactivation together with trichloroacetic acid (TCAA) photodegradation by Cu/Cu2O-ZnO-Fe3O4 were investigated in detail. It was found that Cu/Cu2O-ZnO-Fe3O4 displayed excellent antibacterial activity with a relatively low cytotoxicity concentration due to its synergism of nanowire structure, ion release, and reactive oxygen species generation. Furthermore, the Cu/Cu2O-ZnO-Fe3O4 nanocomposite also exhibited outstanding photocatalytic degradation activity on TCAA under simulated sunlight irradiation, which was verified to be dominated by the surface reaction through kinetic analysis. More interestingly, the cell growth rate of Cu/Cu2O-ZnO-Fe3O4 was determined to be 50% and 10% higher than those of Cu/Cu2O and Cu/Cu2O-ZnO after 10 h incubation, respectively, manifesting a weaker cytotoxicity. Therefore, the designed Cu/Cu2O-ZnO-Fe3O4 could be a promising agent for tap water treatment.

Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy.

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)-photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF-NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH-PT dual magneto-photothermal cancer therapy.

Targeted Dendrimer-Coated Magnetic Nanoparticles for Selective Delivery of Therapeutics in Living Cells.

Nanoparticles are widely used as theranostic agents for the treatment of various pathologies, including cancer. Among all, dendrimers-based nanoparticles represent a valid approach for drugs delivery, thanks to their controllable size and surface properties. Indeed, dendrimers can be easily loaded with different payloads and functionalized with targeting agents. Moreover, they can be used in combination with other materials such as metal nanoparticles for combinatorial therapies. Here, we present the formulation of an innovative nanostructured hybrid system composed by a metallic core and a dendrimers-based coating that is able to deliver doxorubicin specifically to cancer cells through a targeting agent. Its dual nature allows us to transport nanoparticles to our site of interest through the magnetic field and specifically increase internalization by exploiting the T7 targeting peptide. Our system can release the drug in a controlled pH-dependent way, causing more than 50% of cell death in a pancreatic cancer cell line. Finally, we show how the system was internalized inside cancer cells, highlighting a peculiar disassembly of the nanostructure at the cell surface. Indeed, only the dendrimeric portion is internalized, while the metal core remains outside. Thanks to these features, our nanosystem can be exploited for a multistage magnetic vector.

Recyclable metal nanoparticle-immobilized polymer dot on montmorillonite for alkaline phosphatase-based colorimetric sensor with photothermal ablation of Bacteria.

Development of simultaneous bacteria detection and eradication with simple, rapid, and reusable material is important in addressing bacterial contamination issues. In this study, we utilized the expression of alkaline phosphatase (ALP) from bacteria to design fluorescence ON/OFF system for bacteria detection, also using metal oxide nanoparticle for obtaining antibacterial activity and recyclability. The fluorescent-based biosensor with antibacterial activity was prepared by intercalating ALP-sensitive polymer dot (PD) containing ß-cyclodextrin (ß-CD) onto montmorillonite (MMT) as loading matrix via ionic exchange reaction, followed by immobilization of magnetic iron oxide (Fe3O4) and NIR-responsive cesium tungsten oxide (CsWO3). The PD-ßCD-MMT/Fe3O4-CsWO3 nanocomposite exhibited strong fluorescence intensity, which was quenched in the presence of bacterial ALP (0-1000 U/L) due to hydrolysis of p-nitrophenyl phosphate (NPP) into p-nitrophenol (NP) in the hydrophobic site of ß-CD. Furthermore, the nanocomposite could detect both gram-negative Escherichia coli and gram-positive Staphylococcus aureus in the range of 101-107 CFU/mL (LOD 5.09 and 4.62 CFU/mL, respectively), and showed high antibacterial activity against bacteria by generating photothermal heat under 5 min NIR irradiation, causing damage to bacterial cells. This material also demonstrated recyclability via magnetic field exposure due to the presence of Fe3O4. In addition, the fluorescence can be recovered following pH shock and re-conjugation of ß-CD molecules. After 4 cycles, nanocomposite still showed stable photothermal effects and fluorescence-based bacteria detection. Thus, this reusable material offers promising approach for simultaneous bacteria detection and killing, which is simple, rapid, and effective.

A mitochondria-targeting photothermogenic nanozyme for MRI-guided mild photothermal therapy.

Iridium complexes were used as a mitochondria-targeting agent to modify the surface of a photothermogenic nanozyme Fe3O4 nanoparticles (Ir@Fe3O4 NPs). Upon NIR irradiation, Ir@Fe3O4 NPs increase the localized temperature to 42 °C which accelerates the catalysis of ˙OH production from H2O2 resulting in excellent mild photothermal therapy.

Automated microfluidic sorting of mammalian cells labeled with magnetic microparticles for those that efficiently express and secrete a protein of interest.

We developed a method for the fast sorting and selection of mammalian cells expressing and secreting a protein at high levels. This procedure relies on cell capture using an automated microfluidic device handling antibody-coupled magnetic microparticles and on a timed release of the cells from the microparticles after capture. Using clinically compatible materials and procedures, we show that this approach is able to discriminate between cells that truly secrete high amounts of a protein from those that just display it at high levels on their surface without properly releasing it. When coupled to a cell colony imaging and picking device, this approach allowed the identification of CHO cell clones secreting a therapeutic protein at high levels that were not achievable without the cell sorting procedure. Biotechnol. Bioeng. 2017;114: 1791-1802. © 2017 Wiley Periodicals, Inc.

Multi-color magnetic nanoparticle imaging using magnetorelaxometry.

Magnetorelaxometry (MRX) is a well-known measurement technique which allows the retrieval of magnetic nanoparticle (MNP) characteristics such as size distribution and clustering behavior. This technique also enables the non-invasive reconstruction of the spatial MNP distribution by solving an inverse problem, referred to as MRX imaging. Although MRX allows the imaging of a broad range of MNP types, little research has been done on imaging different MNP types simultaneously. Biomedical applications can benefit significantly from a measurement technique that allows the separation of the resulting measurement signal into its components originating from different MNP types. In this paper, we present a theoretical procedure and experimental validation to show the feasibility of MRX imaging in reconstructing multiple MNP types simultaneously. Because each particle type has its own characteristic MRX signal, it is possible to take this a priori information into account while solving the inverse problem. This way each particle type's signal can be separated and its spatial distribution reconstructed. By assigning a unique color code and intensity to each particle type's signal, an image can be obtained in which each spatial distribution is depicted in the resulting color and with the intensity measuring the amount of particles of that type, hence the name multi-color MNP imaging. The theoretical procedure is validated by reconstructing six phantoms, with different spatial arrangements of multiple MNP types, using MRX imaging. It is observed that MRX imaging easily allows up to four particle types to be separated simultaneously, meaning their quantitative spatial distributions can be obtained.

Magnetically-responsive, multifunctional drug delivery nanoparticles for elastic matrix regenerative repair.

Arresting or regressing growth of abdominal aortic aneurysms (AAAs), localized expansions of the abdominal aorta are contingent on inhibiting chronically overexpressed matrix metalloproteases (MMPs)-2 and -9 that disrupt elastic matrix within the aortic wall, concurrent with providing a stimulus to augmenting inherently poor auto-regeneration of these matrix structures. In a recent study we demonstrated that localized, controlled and sustained delivery of doxycycline (DOX; a tetracycline-based antibiotic) from poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), enhances elastic matrix deposition and MMP-inhibition at a fraction of the therapeutically effective oral dose. The surface functionalization of these NPs with cationic amphiphiles, which enhances their arterial uptake, was also shown to have pro-matrix regenerative and anti-MMP effects independent of the DOX. Based on the hypothesis that the incorporation of superparamagnetic iron oxide NPs (SPIONs) within these PLGA NPs would enhance their targetability to the AAA site under an applied external magnetic field, we sought to evaluate the functional effects of NPs co-encapsulating DOX and SPIONs (DOX-SPION NPs) on elastic matrix regeneration and MMP synthesis/activity in vitro within aneurysmal smooth muscle cell (EaRASMC) cultures. The DOX-SPION NPs were mobile under an applied external magnetic field, while enhancing elastic matrix deposition 1.5-2-fold and significantly inhibiting MMP-2 synthesis and MMP-2 and -9 activities, compared to NP-untreated control cultures. These results illustrate that the multifunctional benefits of NPs are maintained following SPION co-incorporation. Additionally, preliminary studies carried out demonstrated enhanced targetability of SPION-loaded NPs within proteolytically-disrupted porcine carotid arteries ex vivo, under the influence of an applied external magnetic field. Thus, this dual-agent loaded NP system proffers a potential non-surgical option for treating small growing AAAs, via controlled and sustained drug release from multifunctional, targetable nanocarriers. STATEMENT OF SIGNIFICANCE: Proactive screening of high risk elderly patients now enables early detection of abdominal aortic aneurysms (AAAs). There are no established drug-based therapeutic alternatives to surgery for AAAs, which is unsuitable for many elderly patients, and none which can achieve restore disrupted and lost elastic matrix in the AAA wall, which is essential to achieve growth arrest or regression. We have developed a first generation design of polymer nanoparticles (NPs) for AAA tissue localized delivery of doxycycline, a modified tetracycline drug at low micromolar doses at which it provides both pro-elastogenic and anti-proteolytic benefits that can augment elastic matrix regenerative repair. The nanocarriers themselves are also uniquely chemically functionalized on their surface to also provide them pro-elastin-regenerative & anti-matrix degradative properties. To provide an active driving force for efficient uptake of intra-lumenally infused NPs to the AAA wall, in this work, we have rendered our polymer NPs mobile in an applied magnetic field via co-incorporation of super-paramagnetic iron oxide NPs. We demonstrate that such modifications significantly improve wall uptake of the NPs with no significant changes to their physical properties and regenerative benefits. Such NPs can potentially stimulate structural repair in the AAA wall following one time infusion to delay or prevent AAA growth to rupture. The therapy can provide a non-surgical treatment option for high risk AAA patients.

Micellar nanocomplexes for biomagnetic delivery of intracellular proteins to dictate axon formation during neuronal development.

During mammalian embryonic development, neurons polarize to create distinct cellular compartments of axon and dendrite that inherently differ in form and function, providing the foundation for directional signaling in the nervous system. Polarization results from spatio-temporal segregation of specific proteins' activities to discrete regions of the neuron to dictate axonal vs. dendritic fate. We aim to manipulate axon formation by directed subcellular localization of crucial intracellular protein function. Here we report critical steps toward the development of a nanotechnology for localized subcellular introduction and retention of an intracellular kinase, LKB1, crucial regulator of axon formation. This nanotechnology will spatially manipulate LKB1-linked biomagnetic nanocomplexes (LKB1-NCs) in developing rodent neurons in culture and in vivo. We created a supramolecular assembly for LKB1 rapid neuronal uptake and prolonged cytoplasmic stability. LKB1-NCs retained kinase activity and phosphorylated downstream targets. NCs were successfully delivered to cultured embryonic hippocampal neurons, and were stable in the cytoplasm for 2 days, sufficient time for axon formation. Importantly, LKB1-NCs promoted axon formation in these neurons, representing unique proof of concept for the sufficiency of intracellular protein function in dictating a central developmental event. Lastly, we established NC delivery into cortical progenitors in live rat embryonic brain in utero. Our nanotechnology provides a viable platform for spatial manipulation of intracellular protein-activity, to dictate central events during neuronal development.

Multifunctional magnetic nanowires: A novel breakthrough for ultrasensitive detection and isolation of rare cancer cells from non-metastatic early breast cancer patients using small volumes of blood.

Circulating tumor cells (CTCs) are recognized as promising biomarkers for diagnosis and indication of the prognosis of several epithelial cancers. However, at present, CTC monitoring is available only for advanced-stage patients rather than for those at an early stage of cancer. This is because of the extraordinary rarity of CTCs and the limited sensitivity of current methods. Herein, we report the development of multifunctional magnetic nanowires for the efficient isolation and detection of CTCs from the blood of patients, especially those with non-metastatic early-stage cancer. The nanowires, which are equipped with a high density of magnetic nanoparticles and five different types of antibodies (Ab mixture_mPpyNWs), offer a significant improvement in cell-isolation efficiency, even from very small amounts of blood (250 µL-1 mL). Notably, CTCs were isolated and identified in 29 out of 29 patients (100%) with non-metastatic early breast cancer, indicating that this procedure allowed detection of CTCs with greater accuracy, sensitivity, and specificity. In addition, we demonstrated in situ "naked eye" identification of the captured cancer cells via a simple colorimetric immunoassay. Our results show that antibody-functionalized magnetic nanowires offer great potential for a broad range of practical clinical applications, including early detection, diagnosis, and treatment of cancer.

Investigating the effect of tumor vascularization on magnetic targeting in vivo using retrospective design of experiment.

Nanocarriers take advantages of the enhanced permeability and retention (EPR) to accumulate passively in solid tumors. Magnetic targeting has shown to further enhance tumor accumulation in response to a magnetic field gradient. It is widely known that passive accumulation of nanocarriers varies hugely in tumor tissues of different tumor vascularization. It is hypothesized that magnetic targeting is likely to be influenced by such factors. In this work, magnetic targeting is assessed in a range of subcutaneously implanted murine tumors, namely, colon (CT26), breast (4T1), lung (Lewis lung carcinoma) cancer and melanoma (B16F10). Passively- and magnetically-driven tumor accumulation of the radiolabeled polymeric magnetic nanocapsules are assessed with gamma counting. The influence of tumor vasculature, namely, the tumor microvessel density, permeability and diameter on passive and magnetic tumor targeting is assessed with the aid of the retrospective design of experiment (DoE) approach. It is clear that the three tumor vascular parameters contribute greatly to both passive and magnetically targeted tumor accumulation but play different roles when nanocarriers are targeted to the tumor with different strategies. It is concluded that tumor permeability is a rate-limiting factor in both targeting modes. Diameter and microvessel density influence passive and magnetic tumor targeting, respectively.

Magnetic Field-Induced Accentuation of Drug Release from Core/Shell Magnetic Mesoporous Silica Nanoparticles for Anticancer Treatment.

Drug (9-aminoacridine) loaded core/shell magnetic iron oxide-containing mesoporous silica nanoparticles (MMSN) were treated with HeLa cells and the drug carriers were agitated by expo- sure to magnetic field. Viability studies show the applicability of drug loaded magnetic material for anticancer treatment, which is enhanced upon stimulation with magnetic field. Confocal micrographs of fluorescein grafted MMSN-treated HeLa cells confirmed the ability of magnetic field to concentrate the synthesized material in the exposed area of the cells. The synthesized material and the applied drug delivery method may find application in magnetic field-responsive targeted treatment of cancer.

Magnetic field-assisted SPR biosensor based on carboxyl-functionalized graphene oxide sensing film and Fe3O4-hollow gold nanohybrids probe.

A novel surface plasmon resonance (SPR) biosensor, coupled with the magnetic bioseparation technique, was constructed and used to the determination of human IgG. Carboxyl-functionalized graphene oxide (cGO) sheet was employed as the sensing film for the efficient immobilization of capture antibody (Ab1). Nanoconjugates (FHAb2), obtained by binding detection antibody (Ab2) to the nanohybrids containing Fe3O4 nanoparticles (Fe3O4 NPs) and hollow gold sphere nanoparticles (HGNPs), were used to specifically collect the target analytes from sample solutions and serve as labels. Owing to the notable plasmonic fields spreading over inner and outer surfaces, HGNPs played key roles in amplifying the SPR response signals originating from the dielectric changes on the sensing films during the binding of Ab1 and human IgG-Ab2FH complexes. In addition, FHAb2 were also used as "vehicles" for the rapid delivery of the separated and enriched target analytes from sample solutions to the sensor surface via an external magnet. In the present method, taking advantages of the magnetic field-driven mass transfer and the significant signal amplification effect of FHAb2, the separation and analysis of human IgG in serum samples are quite effective and sensitive. The limit of detection was 1.88ngmL(-1), which is about 260-fold lower than that obtained by routine SPR biosensors with sandwich assay.

Breast Tumor Targetable Fe3O4 Embedded Thermo-Responsive Nanoparticles for Radiofrequency Assisted Drug Delivery.

Non-invasive radiofrequency (RF) frequency may be utilized as an energy source to activate thermo-responsive nanoparticles for the controlled local delivery of drugs to cancer cells. Herein, we demonstrate that 180 ± 20 nm sized curcumin encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing iron oxide nanoparticles (Fe3O4-CRC-TRC-NPs) were selectively internalized in cancer cells in vivo. Using an RF treatment at 80 watts for 2 min, Fe3O4-CRC-TRC-NPs, dissipated heat energy of 42 degrees C, which is the lower critical solution temperature (LCST) of the chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and apoptosis to cultured 4T1 breast cancer cells. Further, the tumor localization studies on orthotopic breast cancer model revealed that Fe3O4-CRC-TRC-NPs selectively accumulated at the primary tumor as confirmed by in vivo live imaging followed by ex vivo tissue imaging and HPLC studies. These initial results strongly support the development of RF assisted drug delivery from nanoparticles for improved tumor targeting for breast cancer treatment.

Guidance of Magnetic Nanocontainers for Treating Alzheimer's Disease Using an Electromagnetic, Targeted Drug-Delivery Actuator.

The "impermeability" of the blood-brain barrier (BBB) has hindered effective treatment of central nervous system (CNS) disorders such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders. A drug can be delivered to a targeted disease site effectively by applying a strong electromagnetic force to the conjugate of a drug and magnetic nanocontainers. This study developed a novel nanotechnology-based strategy to deliver therapeutic agents to the brain via the BBB as a possible therapeutic approach for AD. First, a novel approach for an electromagnetic actuator for guiding nanocontainers is introduced. Then, we analyzed the in vivo uptake in mice experimentally to evaluate the capacity of the nanocontainers. In the mouse model, we demonstrated that magnetic particles can cross the normal BBB when subjected to external electromagnetic fields of 28 mT (0.43 T/m) and 79.8 mT (1.39 T/m). Our study also assessed the differential effects of pulsed (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of particles across the BBB in mice injected with magnetic nanoparticles (MNPs) via a tail vein. The applied magnetic field was either kept constant or pulsed on and off. Relative to a constant magnetic field, the rate of MNP uptake and transport across the BBB was enhanced significantly by a pulsed magnetic field. Localization inside the brain was established using fluorescent MNPs. These results using 770-nm fluorescent carboxyl magnetic nanocontainers demonstrated the feasibility of the proposed electromagnetic targeted drug delivery actuator. These results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external electromagnetic field. This might be a valuable targeting system for AD diagnosis and therapy.

Selective magnetic resonance imaging of magnetic nanoparticles by acoustically induced rotary saturation.

PURPOSE: The goal of this study was to introduce a new method to selectively detect iron oxide contrast agents using an acoustic wave to perturb the spin-locked water signal in the vicinity of the magnetic particles. The acoustic drive can be modulated externally to turn the effect on and off, allowing sensitive and quantitative statistical comparison and removal of confounding image background variations. METHODS: We demonstrated the effect in spin-locking experiments using piezoelectric actuators to generate vibrational displacements of iron oxide samples. We observed a resonant behavior of the signal changes with respect to the acoustic frequency where iron oxide is present. We characterized the effect as a function of actuator displacement and contrast agent concentration. RESULTS: The resonant effect allowed us to generate block-design "modulation response maps" indicating the contrast agent's location, as well as positive contrast images with suppressed background signal. We found that the acoustically induced rotary saturation (AIRS) effect stayed approximately constant across acoustic frequency and behaved monotonically over actuator displacement and contrast agent concentration. CONCLUSION: AIRS is a promising method capable of using acoustic vibrations to modulate the contrast from iron oxide nanoparticles and thus perform selective detection of the contrast agents, potentially enabling more accurate visualization of contrast agents in clinical and research settings.