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Malaria is a dangerous tropical disease, with high morbidity in developing countries. The responsible parasite has developed resistance to the existing drugs; therefore, new drug delivery systems are being studied to increase efficacy by targeting hemozoin, a parasite paramagnetic metabolite. Herein, magnetic mesoporous silica (magMCM) was synthesized using iron oxide particles dispersed in the silica structure for magnetically driven behavior. The X-ray diffractogram (XRD) and Mössbauer spectra show patterns corresponding to magnetite and maghemite. Furthermore, Mössbauer spectroscopy revealed superparamagnetic behavior, attributed to single magnetic domains in particles smaller than 10 nm. Even in the presence of iron oxide particles, the hexagonal structure of MCM is clearly identified in XRD (low-angle region) and the channels are visible in TEM images. The drug chloroquine (CQ) was encapsulated by incipient wetness impregnation (magMCM-CQ). The N2 adsorption–desorption isotherms show that CQ molecules were encapsulated in the pores, without completely filling the mesopores. BET surface area values were 630 m2 g−1 (magMCM) and 467 m2 g−1 (magMCM-CQ). Encapsulated CQ exhibited rapid delivery (99% in 3 h) in buffer medium and improved solubility compared to the non-encapsulated drug, attributed to CQ encapsulation in amorphous form. The biocompatibility assessment of magMCM, magMCM-CQ, and CQ against MRC5 non-tumoral lung fibroblasts using the MTT assay after 24 h revealed no toxicity associated with magMCM. On the other hand, the non-encapsulated CQ and magMCM-CQ exhibited comparable dose–response activity, indicating a similar cytotoxic effect. [ABSTRACT FROM AUTHOR]

Magnetic Drug Targeting (MDT) is of particular interest to researchers because of its good loading efficiency, targeting accuracy, and versatile use in vivo. Cardiovascular Disease (CVD) is a global chronic disease with a high mortality rate, and the development of more precise and effective treatments is imminent. A growing number of studies have begun to explore the feasibility of MDT in CVD, but an up-to-date systematic summary is still lacking. This review discusses the current research status of MDT from guiding magnetic fields, magnetic nanocarriers, delivery channels, drug release control, and safety assessment. The current application status of MDT in CVD is also critically introduced. On this basis, new insights into the existing problems and future optimization directions of MDT are further highlighted. [ABSTRACT FROM AUTHOR]

AbstractMagnetic Drug Targeting (MDT) is of particular interest to researchers because of its good loading efficiency, targeting accuracy, and versatile use in vivo. Cardiovascular Disease (CVD) is a global chronic disease with a high mortality rate, and the development of more precise and effective treatments is imminent. A growing number of studies have begun to explore the feasibility of MDT in CVD, but an up-to-date systematic summary is still lacking. This review discusses the current research status of MDT from guiding magnetic fields, magnetic nanocarriers, delivery channels, drug release control, and safety assessment. The current application status of MDT in CVD is also critically introduced. On this basis, new insights into the existing problems and future optimization directions of MDT are further highlighted.

Malaria is a dangerous tropical disease, with high morbidity in developing countries. The responsible parasite has developed resistance to the existing drugs; therefore, new drug delivery systems are being studied to increase efficacy by targeting hemozoin, a parasite paramagnetic metabolite. Herein, magnetic mesoporous silica (magMCM) was synthesized using iron oxide particles dispersed in the silica structure for magnetically driven behavior. The X-ray diffractogram (XRD) and Mössbauer spectra show patterns corresponding to magnetite and maghemite. Furthermore, Mössbauer spectroscopy revealed superparamagnetic behavior, attributed to single magnetic domains in particles smaller than 10 nm. Even in the presence of iron oxide particles, the hexagonal structure of MCM is clearly identified in XRD (low-angle region) and the channels are visible in TEM images. The drug chloroquine (CQ) was encapsulated by incipient wetness impregnation (magMCM-CQ). The N2 adsorption–desorption isotherms show that CQ molecules were encapsulated in the pores, without completely filling the mesopores. BET surface area values were 630 m2 g−1 (magMCM) and 467 m2 g−1 (magMCM-CQ). Encapsulated CQ exhibited rapid delivery (99% in 3 h) in buffer medium and improved solubility compared to the non-encapsulated drug, attributed to CQ encapsulation in amorphous form. The biocompatibility assessment of magMCM, magMCM-CQ, and CQ against MRC5 non-tumoral lung fibroblasts using the MTT assay after 24 h revealed no toxicity associated with magMCM. On the other hand, the non-encapsulated CQ and magMCM-CQ exhibited comparable dose–response activity, indicating a similar cytotoxic effect.

Magnetic nanocarriers are nano-platforms that integrate multiple moieties based on magnetic nanoparticles for diagnostic and therapeutic purposes. In recent years, they have become an advanced platform for tumor treatment due to their wide application in magnetic resonance imaging (MRI), biocatalysis, magneto-thermal therapy (MHT), and photoresponsive therapy. Drugs loaded into magnetic nanocarriers can efficiently be directed to targeted areas by precisely reshaping their structural properties. Magnetic nanocarriers allow us to track the location of the therapeutic agent, continuously control the therapeutic process and eventually assess the efficacy of the treatment. They are typically used in synergistic therapeutic applications to achieve precise and effective tumor treatment. Here we review their latest applications in tumor treatment, including stimuli-responsive drug delivery, MHT, photoresponsive therapy, immunotherapy, gene therapy, and synergistic therapy. We consider reducing toxicity, improving antitumor efficacy, and the targeting accuracy of magnetic nanocarriers. The challenges of their clinical translation and prospects in cancer therapy are also discussed.

Magnetic nanocarriers have been extensively used as a potential drug release system for breast cancer therapy. This work investigates drug release kinetics and transport mechanisms of dasatinib (DAS) anticancer drugs encapsulated in nanomagnetic self-assembled micelles. The drug release kinetics of DAS from the nanomagnetic micelles (NMM) was predicted by fitting the drug release experimental data to four different empirical models at pH values 7.4 and 5. Moreover, a simple mathematical model that can predict the drug release from bulk eroding polymer matrices has been developed using the COMSOL Multiphysics® program. The diffusional egress of the DAS release through the NMM was carried out by evaluating the diffusion coefficients inside NMM using Fick's second law and diffusion coefficients in the solution utilizing the Stokes-Einstein equation. The results revealed that NMM exhibited a superior sustained drug release rate in acidic conditions compared to the neutral state. The Peppas-Sahlin and COMSOL models gave the best fitting for the experimental drug release data and eroding matrices obtained from free DAS, DAS-micelles, and DAS-magnetic micelles at both pH values with correlation coefficients reached to 0.99. The transport mechanisms results showed a Fickian diffusion mechanism controlled with the highest diffusion coefficients of NMM in acidic conditions, while a significant relaxation contribution was observed at the neutral state. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are known as killer diseases and to overcome these diseases, novel approaches are needed. Although many approaches were able to control this disease, they still had high risks for the patients. One of the best ways to control CVDs is to use targeted Nanosystems, with the help of Nanotechnology and Biology Sciences. Despite current therapeutic strategies to reduce risk, patients still experience the consequences of CVD. Improve visualization of early atherosclerotic lesions to decrease residual CVD risk is one of its goals. Nanomaterials used as Nanocarriers are mainly Polymeric based, Magnetic, Metalic, Silica based and Liposomes. In addition, some drugs can be loaded to these Nanocarries. In this review, we focused on nanocarriers to manage Atherosclerosis, which is the most prevalent type of CVD. We divided these nanocarriers into five main groups: Polymeric nanocarriers, Magnetic nanocarriers, Metalic nanocarriers, Liposomes and Silica-based nanocarriers. [ABSTRACT FROM AUTHOR]

The present study introduces the process performances of nitrophenols pertraction using new liquid supported membranes under the action of a magnetic field. The membrane system is based on the dispersion of silver–iron oxide nanoparticles in n-alcohols supported on hollow microporous polypropylene fibers. The iron oxide–silver nanoparticles are obtained directly through cyclic voltammetry electrolysis run in the presence of soluble silver complexes ([AgCl2]−; [Ag(S2O3)2]3−; [Ag(NH3)2]+) and using pure iron electrodes. The nanostructured particles are characterized morphologically and structurally by scanning electron microscopy (SEM and HFSEM), EDAX, XRD, and thermal analysis (TG, DSC). The performances of the nitrophenols permeation process are investigated in a variable magnetic field. These studies show that the flux and extraction efficiency have the highest values for the membrane system embedding iron oxide–silver nanoparticles obtained electrochemically in the presence of [Ag(NH3)2]+ electrolyte. It is demonstrated that the total flow of nitrophenols through the new membrane system depends on diffusion, convection, and silver-assisted transport.

Graphical abstract Highlights • ALPs were purified by a novel magnetic nanocarriers from bovine skim milk. • Vanadate and phosphate salts were immobilized on the BMNP. • ALPs were purified with the affordable method. Abstract Modified Fe 3 O 4 magnetic nanoparticles (magnetic nanocarrier) technology have found the proper place in separation and purification techniques, such as protein and enzyme purification, mostly due to its easy and fast operational procedure by using an external permanent magnet. Herein, Fe 3 O 4 magnetic nanoparticles were prepared, and surface modification was performed with vanadate and phosphate salts to yield four various model of magnetic nanocarriers. Affinity ligands which are used for immobilization on the nanocarriers leading to the development of appropriative nanocarriers for the affinity separation of alkaline phosphatase from the bovine milk. The findings showed that the use of sodium hexametaphosphate affinity ligand attached to the carrier with an 18-atom linker leads to better separation of alkaline phosphatase from the bovine milk with 14.1-fold purification efficiency. All results confirmed that our designed nanocarriers can purify alkaline phosphatase using a fast and low-cost approach. [ABSTRACT FROM AUTHOR]

Currently, modified Fe 3 O 4 magnetic nanoparticles frequently are used as nanocarriers for proteins and enzymes purification. In the present study, Fe 3 O 4 magnetic nanoparticles were prepared, and their surfaces were modified with p -aminophenol affinity ligand immobilized by different linkers. The modified nanocarriers were used for the purification of α-amylase from the bovine milk (after precipitation the casein) by affinity purification. To evaluate the effectiveness of the p -aminophenol modified magnetic nanocarriers, the three different types of nanocarriers with different linkers having varying lengths were prepared. All nanocarriers were characterized and validated using FT-IR, SEM, EDX, VSM and XRD analysis methods According to our results, p -aminophenol ligand attached to the nanocarrier by long linkers better separates the α-amylase from the casein free skim milk with 49.66% recovery and 48.18-fold purification efficiency. The results of this study showed that our novel magnetic nanocarriers have the capacity to be used for fast, reproducible and cost-effective purification of α-amylase. [ABSTRACT FROM AUTHOR]

Recent studies of magnetic carrier technology have focused on its applications in separation and purification technologies, due to easy separation of the target from the reaction medium by applying an external magnetic field. In the present study, Fe 3 O 4 superparamagnetic nanoparticles were prepared to utilize a chemical co-precipitation method, then the surfaces of the nanoparticles were modified with arsanilic acid derivatives which were used as the specific nanocarriers for the affinity purification of alkaline phosphatase from the hen's egg yolk. The six different types of magnetic nanocarriers with varied lengths of the linkers were obtained. All samples were characterized step by step and validated using FTIR, SEM, EDX, VSM and XRD analysis methods As the results were shown, the use of inflexible tags with long linkers on the surface of the nanocarrier could lead to better results for separation of alkaline phosphatase from the hen's egg yolk with 76.2% recovery and 1361.7-fold purification. The molecular weight of the purified alkaline phosphatase was estimated to be 68 kDa by SDS–PAGE. The results of this study showed that the novel magnetic nanocarriers were capable of purifying alkaline phosphatase in a practically time and cost effective way. [ABSTRACT FROM AUTHOR]

Magnetic nanocarriers are nano-platforms that integrate multiple moieties based on magnetic nanoparticles for diagnostic and therapeutic purposes. In recent years, they have become an advanced platform for tumor treatment due to their wide application in magnetic resonance imaging (MRI), biocatalysis, magneto-thermal therapy (MHT), and photoresponsive therapy. Drugs loaded into magnetic nanocarriers can efficiently be directed to targeted areas by precisely reshaping their structural properties. Magnetic nanocarriers allow us to track the location of the therapeutic agent, continuously control the therapeutic process and eventually assess the efficacy of the treatment. They are typically used in synergistic therapeutic applications to achieve precise and effective tumor treatment. Here we review their latest applications in tumor treatment, including stimuli-responsive drug delivery, MHT, photoresponsive therapy, immunotherapy, gene therapy, and synergistic therapy. We consider reducing toxicity, improving antitumor efficacy, and the targeting accuracy of magnetic nanocarriers. The challenges of their clinical translation and prospects in cancer therapy are also discussed. [Display omitted] • Diverse studies are reviewed for potential clinical applications of magnetic nanocarriers in tumor therapy. • The latest design strategies of magnetic nanocarriers for improving antitumor efficacy and targeting accuracy are presented. • Solutions required to move magnetic nanocarriers from bench top to bedside are discussed. [ABSTRACT FROM AUTHOR]

In recent decades, targeted drug delivery systems for breast cancer treatment emerged as an ideal alternative and promising solution to reduce systemic side effects of chemotherapeutic agents. In this study, the preparation and characterization of cationic doxorubicin (DOX) loaded magnetic dextran-spermine (DEX-SP) nanocarriers (DEX-SP-DOX) by ionic gelation were fully investigated. Then, anti-HER2 as a monoclonal antibody (mAb) and targeting ligand was conjugated via EDC/NHS reagents. The binding was confirmed by Bradford assay and further assessments were carried out by size and zeta potential measurements. Cytotoxicity effect and internalization of magnetic nanocarriers were assessed by MTT and Prussian blue assays and transmission electron microscopy (TEM), respectively. DLS measurements indicated that the size of nanocarriers increased from 62 to 84 nm by conjugation of anti-HER2 to them. The in vitro release of DOX from mAb conjugated magnetic nanocarriers at pHs 5 and 7.4 was found to be 85 and 55.5%, respectively. The MTT and Prussian blue assays demonstrated enhanced and selective uptake of DEX-SP-DOX-mAb by SKBR cell (HER2 overexpressed cells) in comparison with unconjugated nanocarriers due to higher cellular binding. The TEM result also confirmed cellular internalization of DEX-SP-DOX-mAb magnetic nanocarriers. These results are very promising for targeted delivery of DOX to HER2 positive breast cancer cells. [ABSTRACT FROM AUTHOR]

In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, FeO-NH, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/ N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release. [ABSTRACT FROM AUTHOR]

A novel magnetic nanocarrier was strategically designed and successfully prepared. Phot0sensitizer 2, 7, 12, 18 - tetramethyl - 3, 8 - di -(1 - propoxyethyl)- 13, 17 - bis - (3 - hydroxypropyl) porphyrin (PHPP) was encapsulated into polylactic acid (PLA)- coated Fe304 nanoparticles. The diameter of nanocarrier is 30 - 50 nm by transmission electron micrograph (TEM). The encapsulation efficiency of photosensitizer is 27.98% calculated from UV - vis absorption spectra. The nanocarrier shows obvious photocytotoxic activity to Hela299 tumor cells in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Purpurin-18 loaded magnetic silica nanocarriers for photodynamic therapy (PDT) were prepared in cottonseed oil by W/O micro-emulsion method. The size of the nanocarriers was ranged from 20 to 30 nm obtained from transmission electron micrograph observation. The photodynamic drug purpurin-18 was successfully enwrapped in the nanocarriers characterized by ultraviolet–visible absorption and Fourier transform infrared spectroscopy spectra. The generation of singlet oxygen (1O2) was followed by N,N-dimethyl-4-nitrosoaniline (RNO) bleaching assay. The loss of RNO absorbance at 440 nm versus irradiation time displayed that purpurin-18 could play a role in normal. [Copyright &y& Elsevier]

[Display omitted] • Starch-based magnetic nanocapsules were successfully synthesized for drug delivery. • A core-shell morphology was obtained, with an average diameter of 143 nm. • The nanocomposite showed no death (in vivo experiments) and in vitro antitumor activity. • Release studies demonstrated a prolonged drug release profile. Magnetic nanocomposites were synthesized for the targeted delivery of hydrophilic bioactives through guidance generated by a magnetic field. Superparamagnetic iron oxide nanoparticles (SPIONs) were used to generate hydroxyethyl starch magnetic nanocapsules (HES MNCs). This synthesis allowed the co-encapsulation of oncocalyxone A (onco A) and surface-modified magnetite nanoparticles (Fe 3 O 4 @citrate) into the same nanostructure. The synthesized nanocapsules exhibited a core-shell morphology, with an average diameter of 143 nm. This nanocomposite showed potential anticancer activity (IC 50) against four human tumor cell lines: glioblastoma SNB-19 (1.010 μgmL−1), colon carcinoma HCT-116 (2.675 μgmL−1), prostate PC3 (4.868 μgmL−1), and leukemia HL-60 (2.166 μgmL−1). Additionally, in vivo toxicity and locomotor activity were evaluated in a zebrafish (Danio rerio) model. The nanocomposite exhibited in vitro cytotoxicity, prolonged drug release profile and also responded to an applied magnetic field, representing a versatile compound with perspectives for highest concentration of different hydrophilic bioactives in a target tissue through magnetic vectorization. [ABSTRACT FROM AUTHOR]

The present study introduces the process performances of nitrophenols pertraction using new liquid supported membranes under the action of a magnetic field. The membrane system is based on the dispersion of silver–iron oxide nanoparticles in n-alcohols supported on hollow microporous polypropylene fibers. The iron oxide–silver nanoparticles are obtained directly through cyclic voltammetry electrolysis run in the presence of soluble silver complexes ([AgCl2]−; [Ag(S2O3)2]3−; [Ag(NH3)2]+) and using pure iron electrodes. The nanostructured particles are characterized morphologically and structurally by scanning electron microscopy (SEM and HFSEM), EDAX, XRD, and thermal analysis (TG, DSC). The performances of the nitrophenols permeation process are investigated in a variable magnetic field. These studies show that the flux and extraction efficiency have the highest values for the membrane system embedding iron oxide–silver nanoparticles obtained electrochemically in the presence of [Ag(NH3)2]+ electrolyte. It is demonstrated that the total flow of nitrophenols through the new membrane system depends on diffusion, convection, and silver-assisted transport. [ABSTRACT FROM AUTHOR]

Abstract: We propose the use of functionalized superparamagnetic nanoparticles for capturing, and transporting analytes, in association with an external miniature magnet to deposit such nanocarrier species at the electrode surface. This approach can be employed for the electroanalytical determination of chemical species capable of interacting with the nanoparticles, or in the opposite case, to block their response at the electrode surface. The concept was successfully demonstrated by using aminofunctionalized nanoparticles to block the discharge of hexacyanoferrate(II) ions, and to enhance the signals of aquapentacyanoferrate(II) ions via coordination to the surface amino groups. Selective analysis was also performed for silver ions, surpassing the stripping methods in terms of versatility and usefulness. [Copyright &y& Elsevier]

Magnetically-assisted delivery of therapeutic agents to the site of interest, which is referred to as magnetic drug targeting, has proven to be a promising strategy in a number of studies. One of the key advantages over other targeting strategies is the possibility to control remotely the distribution and accumulation of the nanocarriers after parenteral administration. However, preparation of effective and robust magnetically responsive nanocarriers based on superparamagnetic iron oxide nanocrystals (SPIONs) still represents a great scientific challenge, since spatial guidance of individual SPIONs is ineffective despite the presence of high magnetic field gradient. A strategy to overcome this issue is the clustering of SPIONs to achieve sufficient magnetic responsiveness. In this mini-review, we address current and future strategies for the design and fabrication of magnetically responsive nanocarriers based on SPIONs for magnetically-targeted drug delivery, including the underlying physical requirements, the possibility of drug loading, and the control of drug release at the targeted site., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel approach was developed for the coencapsulation of an anti-HIV drug (tenofovir) and a latency-breaking agent (vorinostat), using magnetically guided layer-by-layer (LbL) assembled nanocarriers for the treatment of neuroAIDS. Ultrasmall iron oxide (Fe3O4) nanoparticles (10±3 nm) were synthesized and characterized. The LbL technique was used to achieve a sustained release profile, and application of 2 bilayers ([tenofovir+dextran sulphate]2+vorinostat) to magnetic nanoparticles resulted in a 2.8 times increase in drug (tenofovir) loading and also resulted in an increase in the drug release period by 30-fold, with 100% drug release in sustained manner over a period of 5 days with the simultaneous stimulation of latent HIV expression. Nanoformulation showed a good blood-brain barrier transmigration ability (37.95%±1.5%) with good in vitro antiviral efficacy (~33% reduction of p24 level) over a period of 5 days after HIV infection in primary human astrocytes, with good cell viability (>90%). Hence, LbL arrangements of drugs on magnetic nanoparticles provides sustained release and, therefore, may improve the patient's adherence to therapy and lead to better compliance.

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe(3)O(4) magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15-25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.