Magnetic nanoparticle drug targeting to patient-specific atherosclerosis: effects of magnetic field intensity and configuration

Nanoparticle-mediated drug delivery is recognized as a promising option for targeted treatment of atherosclerosis. In this paper, the Eulerian-Lagrangian technique is adopted to simulate the delivery of drug-loaded nanoparticles to patient-specific atherosclerotic plaque with the aid of an external magnetic field. Plaques and vascular walls are introduced as porous media formulated by the Darcy-Forchheimer model in this targeted transport process. The results demonstrate that the delivery efficiency of particles to atherosclerosis depends on the external magnetic field, such as configuration and intensity, in which the configuration angle of the current wire is a key factor and the double current wires have advantages over the single current wire. Meanwhile, the delivery efficiency gradually decreases as the distance between the plaque cap and the current wire increases. Further, although augmenting the current or magnetic susceptibility can generally improve the delivery efficiency of nanoparticles, this increase is not apparent when small-sized nanoparticles are employed as drug transport particles. The results obtained can potentially serve as the guideline to optimize regimens for the targeted therapy of atherosclerosis.

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.

Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.

Experimental study on magnetic drug targeting in treating cholangiocarcinoma based on internal magnetic fields

Objective: To evaluate the effect of magnetic nanoparticle containing 5-fluorouracil (5-FU) targeting in treating chol- angiocarcinoma based on internal magnetic fields built inside the tumor. Methods: 32 nude mice of BABL/C bearing ectopic tumor were built by subcutaneouly injecting cholangiocarcinoma cell line QBC 939. Three weeks after tumor inoculation, the animal models were divided equally into four groups at random including: (a) group A, consisting of internal magnetic field built by magnetic biliary stent wires inserted into tumor tissue and receiving magnetic nanoparticles containing 5-FU administered via tail vein injection at 250 mg/kg for consecutive five days; (b) group B, receiving placebo (sodium chloride); (c) group C, receiving pure magnetic biliary stent wires without the applying of magnetic nanoparticles; (d) group D, consisting of external magnetic fields and the same treatment of magnetic nanoparticles containing 5-FU as group A. The tumor volumes were measured every 3 days, totally six times from treatment started. Tumor tissues were observed by transmission electron microscope when the nude mice were killed after the observation period. Results: The experimental group (group A) showed significantly therapeutic efficacy. Moreover, apoptosis of tumor cells could be easily detected in this group. Conclusion: Magnetic particles containing 5-FU combined with internal magnetic field can effectively treat cholangiocarcinoma, and its therapeutic efficacy is better than that of the traditional method based on external magnetic fields.

Functionalized magnetic nanoparticles for drug delivery in tumor therapy

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles(MNPs) have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.

Study on Tat Mediated Magnetic Nanoparticles Having Composite Targeting Function

This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as a drug carrier, Methotrexate (MTX) was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75 nm were prepared and characterized by TEM, AFM and VSM.The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity.

Performance Analysis of Magnetic Nanoparticles during Targeted Drug Delivery:Application of OHAM

In recent years,the emergence of nanotechnology experienced incredible development in the field of medical sciences.During the past decade,investigating the characteristics of nanoparticles during fluid flow has been one of the intriguing issues.Nanoparticle distribution and uniformity have emerged as substantial criteria in both medical and engineering applications.Adverse effects of chemotherapy on healthy tissues are known to be a significant concern during cancer therapy.A novel treatment method of magnetic drug targeting(MDT)has emerged as a promising topical cancer treatment along with some attractive advantages of improving efficacy,fewer side effects,and reduce drug dose.During magnetic drug targeting,the appropriate movement of nanoparticles(magnetic)as carriers is essential for the therapeutic process in the blood clot removal,infection treatment,and tumor cell treatment.In this study,we have numerically investigated the behavior of an unsteady blood flowinfused with magnetic nanoparticles during MDT under the influence of a uniform external magnetic field in a microtube.An optimal homotopy asymptotic method(OHAM)is employed to compute the governing equation for unsteady electromagnetohydrodynamics flow.The influence of Hartmann number(Ha),particle mass parameter(G),particle concentration parameter(R),and electro-osmotic parameter(k)is investigated on the velocity of magnetic nanoparticles and blood flow.Results obtained show that the electro-osmotic parameter,along with Hartmann’s number,dramatically affects the velocity of magnetic nanoparticles,blood flow velocity,and flow rate.Moreover,results also reveal that at a higher Hartman number,homogeneity in nanoparticles distribution improved considerably.The particle concentration andmass parameters effectively influence the capturing effect on nanoparticles in the blood flow using a micro-tube for magnetic drug targeting.Lastly,investigation also indicates that the OHAM analysis is efficient and quick to handle the system of nonlinear equations.

Construction of multi-functional delivery system: transferrin mediated tat and drug-loaded magnetic nanoparticles

This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan (O-CMC) as drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as drug carriers, Methotrexate (MTX) was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75nm were prepared and characterized by TEM, AFM and VSM. The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity; additionally, sustained release of MTX from O-CMC nanoparticles was observed in vitro, suggesting that the O-MNPs-Tat-Tf could be a novel magnetic targeting carrier. We also studied the ability of O-MNPs-Tat-Tf crossing BBB in rats by single photon emission computed tomography (SPECT).

Dynamics of magnetic microbubble transport in blood vessels

Magnetic microbubbles(MMBs)can be controlled and directed to the target site by a suitable external magnetic field,and thus have potential in therapeutic drug-delivery application.However,few studies focus on their dynamics in blood vessels under the action of magnetic and ultrasonic fields,giving little insight into the mechanism generated in diagnostic and therapeutic applications.In this study,equations of MMBs were established for simulating translation,radial pulsation and the coupled effect of both.Meanwhile,the acoustic streaming and shear stress on the vessel wall were also presented,which are associated with drug release.The results suggest that the magnetic pressure increases the bubble pulsation amplitude,and the translation coupled with pulsation is manipulated by the magnetic force,causing retention in the target area.As the bubbles approach the vessel wall,the acoustic streaming and shear stress increase with magnetic field enhancement.The responses of bubbles to a uniform and a gradient magnetic field were explored in this work.The mathematical models derived in this work could provide theoretical support for experimental phenomena in the literature and also agree with the reported models.

磁场和超声波共同作用下磁性微球的深度聚集

在磁性药物靶向治疗中,由于普通电磁铁产生的磁场的磁通密度会随距离衰减,造成磁性药物颗粒在离磁极较近的部位聚集较多,而在离磁极较远的部位聚集较少,这限制了磁靶向技术在深度组织部位的应用.提出了环形磁极磁场和超声波声场相结合的非侵入性新方法,以实现磁性微粒的三维深度聚集.首先,给出深度聚集磁性微粒实验设备的结构设计;然后,利用COMSOL仿真软件计算出实现深度聚集的超声波振幅范围;最后,依据仿真结果给出的参数进行了实验.实验结果证明,在合适的超声波强度下,磁性微球在远离磁极区域的聚集量多于离磁极较近区域,实现了磁性微粒在三维方向的深度聚集.

MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery

Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise manipulation.The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery.Here,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted therapy.Our approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during manipulation.We select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive decomposition.Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under actuation.Tuning the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental variations.Transported to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in vivo.Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.

Iron oxide nanoparticles in magnetic drug targeting and ferroptosis-based cancer therapy

Iron oxide(IO)nanoparticles(NPs)have gained significant attention in the field of biomedicine,particularly in drug targeting and cancer therapy.Their potential in magnetic drug targeting(MDT)and ferroptosis-based cancer therapy is highly promising.IO NPs serve as an effective drug delivery system(DDS),utilizing external magnetic fields(EMFs)to target cancer cells while minimizing damage to healthy organs.Additionally,IO NPs can generate reactive oxygen species(ROS)and induce ferroptosis,resulting in cytotoxic effects on cancer cells.This article explores how IO NPs can potentially revolutionize cancer research,focusing on their applications in MDT and ferroptosis-based therapy.

Application of Paclitaxel-loaded EGFR Peptide-conjugated Magnetic Polymeric Liposomes for Liver Cancer Therapy

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic polymeric liposome(MPL)nanoparticles(NPs)assembled from octadecyl quatemized carboxymethyl chitosan(OQC),PEGylated OQC,cholesterol,and magnetic NPs,and functionalized with epithelial growth factor receptor(EGFR)peptide,were successfully prepared for in-vivo liver targeting.The two-step liver targeting strategy,based on both magnetic force and EGFR peptide conjugation,was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse.The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force,but could also diffuse into tumor cells as a result of EGFR targeting.In addition,paclitaxel(PTX)was incorporated into small EGFR-conjugated MPLs(102.0土0.7 nm),resulting in spherical particles with high drug encapsulation efficiency(>90%).The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels.In conclusion,PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

Magnetic nanoparticle-based cancer therapy

Nanoparticles（NPs） with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles（MNPs） that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging（MRI） monitoring cancer therapy and magnetic tissue engineering are also addressed.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

基于磁纳米粒子治疗恶性骨肿瘤的研究进展

恶性骨肿瘤包括原发性肿瘤和转移性肿瘤,具有高致残率、高复发率、高死亡率的特点。传统的手术、放化疗等手段虽然能一定程度上提高恶性骨肿瘤治疗效果,但仍存在肿瘤复发率高、药物局部作用较弱、全身副作用较大等限制。新兴的磁靶向技术可以有效解决局部药物浓度不足的难题。通过磁场引导,磁性纳米粒子可以在肿瘤病灶部位聚集,发挥肿瘤治疗作用。本文总结了磁性纳米粒子在骨肿瘤治疗中的应用进展,为后续磁性纳米粒子在恶性骨肿瘤治疗中的研究起到一定的借鉴和参考意义。

A new kind of magnetic targeting induction heating drug carrier and its physical and biological properties

Nano-carbon and iron composite—carbon-coated iron nanoparticles (CCINs) produced by carbon arc method can be used as a new kind of magnetic targeting induction heating drug carrier for cancer therapy. The structure and morphology of CCINs are studied by X-ray diffraction (XRD) and transmission electron microscope (TEM). Mossbauer spectra of these nanoparticles show that they contain only iron and carbon, without ferric carbide and ferric oxide. CCINs can be used as the magnetic drug carrier, with the effect of targeting magnetic induction heating in its inner core and higher drug adsorption in its nano-carbon shell outside because of its high specific surface area. CCINs can absorb Epirubicin (EPI) of 160 μg/mg measured by an optical spectrometer. In acute toxicity experiment with mice, the median lethal dose (LD50) of EPI is 16.9 mg/kg, while that of EPI-CCINs mixture is 20.7 mg/kg and none of the mice died after pure CCINs medication. The results show that pure CCINs belong to non-toxic grade and EPI delivery in mixture with CCINs can reduce its acute toxicity in mice. The magnetic properties of CCINs and their magnetic induction heating are investigated. The iron nanoparticle in its inner core has better magnetism with a good effect on targeting magnetic induction heating. When the CCINs are mixed with physiological salt water and are injected uniformly in pig’s liver, the temperature goes up to 48°C. While in the case that CCINs are filled in a certain section of pig’s liver, the temperature goes up to 52°C. In both cases the temperature is high enough to kill the cancer cell. CCINs have potential applications in cancer therapy.

磁性微球的生物医学应用研究进展

磁性微球作为一种新型功能材料 ,在生物医学、细胞学和生物工程学等领域被广泛地应用于生物目标产品的快速分离 ;在临床医学方面被广泛应用于靶向给药。

磁性壳聚糖微球的制备、表征及其靶向给药研究

质量分数为 1 0 %的壳聚糖溶液通过乳液法与戊二醛交联合成了壳聚糖微球 ( CM) ,在其表面吸附一层 Fe3 O4制得磁性壳聚糖微球 ( MCM)。用扫描电镜、红外光谱仪、原子吸收分光光度计和紫外吸收分光光度计对合成的高分子微球进行了形貌观察和结构表征。结果表明 ,降低壳聚糖的分子量 ,有利于合成单分散性好、粒径小 ( <1 μm)的微球 ;体外测试表明 ,CM包封阿斯匹林 ( AS)微球 ( CM-AS)在 1 h内释药量达 4 0 % ,而MCM-AS仅为 1 5 % ,CM-AS和 MCM-AS释药量达 5 0 %的时间分别为 1 .4和 5 h;MCM和 MCM-AS均具有较强的磁性 ,后者在外磁场作用下能够实现靶向给药。