Delivery Of Magnetic Nanoparticles Research Articles

Selective delivery of neuropeptide Y peptides linked to magnetic particles for hyperthermia application

Although standard treatments against cancer have achieved significant effects in growth inhibition and tumor elimination, they still cause severe side effects. Therefore, the specific targeting of cancer cells without affecting healthy tissue is currently an important desire in cancer therapy. Cell surface receptors that bind peptides are often overexpressed on tumor cells and can therefore be considered promising targets for selective tumor therapy. Here, we report on the use of neuropeptide Y receptor 1 (Y1R) specific delivery of magnetic nanoparticles. The Y1R is overexpressed in breast cancer cells including triple negative type tumors. Magnetic particles allow for hyperthermia applications for the treatment of malignant cells and have been proposed for biomedical use for several years. One of the limitations so far was selectivity and intracellular uptake into tumor cells. By using specifically modified nanoparticles and site-specific conjugation to selective peptides specific uptake into Y1R positive cells is demonstrated here.

Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review.

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

Mild magnetic hyperthermia-activated immuno-responses for primary bladder cancer therapy

Surgical intervention followed by chemotherapy is the principal treatment strategy for bladder cancer, which is hindered by significant surgical risks, toxicity from chemotherapy, and high rates of recurrence after surgery. In this context, a novel approach using mild magnetic hyperthermia therapy (MHT) for bladder cancer treatment through the intra-bladder delivery of magnetic nanoparticles is presented for the first time. This method overcomes the limitations of low magnetic thermal efficiency, inadequate tumor targeting, and reduced therapeutic effectiveness associated with the traditional intravenous administration of magnetic nanoparticles. Core-shell Zn–CoFe2O4@Zn–MnFe2O4 (MNP) nanoparticles were developed and further modified with hyaluronic acid (HA) to enhance their targeting ability toward tumor cells. The application of controlled mild MHT using MNP-HA at temperatures of 43–44 °C successfully suppressed the proliferation of bladder tumor cells and tumor growth, while also decreasing the expression levels of heat shock protein 70 (HSP70). Crucially, this therapeutic approach also activated the body's innate immune response involving macrophages, as well as the adaptive immune responses of dendritic cells (DCs) and T cells, thereby reversing the immunosuppressive environment of the bladder tumor and effectively reducing tumor recurrence. This study uncovers the potential immune-activating mechanism of mild MHT in the treatment of bladder cancer and confirms the effectiveness and safety of this strategy, indicating its promising potential for the clinical management of bladder cancer with a high tendency for relapse.

External magnet-guided targeted delivery and tissue distribution analysis of anti-cluster of differentiation 3 conjugated magnetic nanoparticles of Fe3O4 using in vivo imaging system

Drug distribution is a vital parameter for depicting the pharmacokinetic properties of therapeutic agents. Magnetic nanoparticles (MNPs) conjugated with anti-cluster of differentiation 3 (anti-CD3) monoclonal antibody (MNPs-Ab) is a promising immunotherapeutic agent. Magnet-guided targeted delivery of MNPs has been studied exclusively in oncology. The distribution of MNPs is routinely analyzed by measuring Fe levels using inductively coupled mass spectrometry (ICP-MS). However, the ICP-based methods measure the total iron content, including endogenous iron. We used an efficient approach that measured MNPs-Ab distribution after intravenous administration using an in vivo imaging system. The fluorescent-labeled anti-CD3s are conjugated with dextran-coated magnetic nanoparticles (50 nm diameter) by the glutaraldehyde conjugation method. MNPs-Ab was intravenously administered to BALB/c mice. The fluorescence intensity in live animal and organs were analyzed after 0, 1, and 24 h. The conjugation of fluorescently labeled antibodies with MNPs was validated. The attachment of a permanent magnet on the dorsal skin area successfully guided the intravenously injected Ab-MNPs within 24 h. However, after 1 h, no observable fluorescence was seen at the target site. The in vitro organ distribution study confirms nanoparticles’ predominant distribution in the liver and kidneys-the intensities of the fluorescence increase after 24 h than 1 h. Our in vivo imaging studies confirmed the external magnet-driven targeted distribution of the antibody-conjugated nanoparticle. Besides, the in vivo imaging system enables rapidly identifying the distributed nanoparticles.

Improved tumour delivery of iron oxide nanoparticles for magnetic hyperthermia therapy of melanoma via ultrasound guidance and 111In SPECT quantification.

Magnetic field hyperthermia relies on the intra-tumoural delivery of magnetic nanoparticles by interstitial injection, followed by their heating on exposure to a remotely-applied alternating magnetic field (AMF). This offers a potential sole or adjuvant route to treating drug-resistant tumours for which no alternatives are currently available. However, two challenges in nanoparticle delivery currently hinder the effective clinical translation of this technology: obtaining enough magnetic material within the tumour to enable sufficient heating; and doing this accurately to limit or avoid damage to surrounding healthy tissue. A further complication is the lack of established methods to non-invasively quantify nanoparticle biodistribution, which is necessary to evaluate the performance of improved delivery strategies. Here we employ 111In radiolabelling and single-photon emission computed tomography (SPECT) to non-invasively quantify distribution of a clinical grade iron-oxide-based nanoparticle in a mouse model of melanoma. We show that compared to manual injection, ultrasound guided delivery together with syringe-pump-controlled infusion improves both the nanoparticle concentration within the tumour, and the accuracy of delivery - reducing off-target peri-tumoural delivery. Following AMF heating, injected melanomas shrank significantly compared to non-injected controls, validating therapeutic efficacy. Systemic off-target delivery was quantified and extrapolated to predict off-target energy absorbance within safe limits for the main sites of background accumulation. With many nanoparticle-based therapies currently in development for cancer, this image-guided delivery strategy has wide potential impact beyond the field of magnetic hyperthermia. Future use in representative patient cohorts would also be enabled by the high clinical availability of both SPECT and ultrasound imaging.

Neutrophil as a Carrier for Cancer Nanotherapeutics: A Comparative Study of Liposome, PLGA, and Magnetic Nanoparticles Delivery to Tumors.

Insufficient drug accumulation in tumors is still a major concern for using cancer nanotherapeutics. Here, the neutrophil-based delivery of three nanoparticle types-liposomes, PLGA, and magnetite nanoparticles-was assessed both in vitro and in vivo. Confocal microscopy and a flow cytometry analysis demonstrated that all the studied nanoparticles interacted with neutrophils from the peripheral blood of mice with 4T1 mammary adenocarcinoma without a significant impact on neutrophil viability or activation state. Intravital microscopy of the tumor microenvironment showed that the neutrophils did not engulf the liposomes after intravenous administration, but facilitated nanoparticle extravasation in tumors through micro- and macroleakages. PLGA accumulated along the vessel walls in the form of local clusters. Later, PLGA nanoparticle-loaded neutrophils were found to cross the vascular barrier and migrate towards the tumor core. The magnetite nanoparticles extravasated in tumors both via spontaneous macroleakages and on neutrophils. Overall, the specific type of nanoparticles largely determined their behavior in blood vessels and their neutrophil-mediated delivery to the tumor. Since neutrophils are the first to migrate to the site of inflammation, they can increase nanodrug delivery effectiveness for nanomedicine application.

Tumor size dependent MNP dose evaluation in realistic breast tumor models for effective magnetic hyperthermia

The goal of the current investigation is to determine the breast tumor size-dependent MNP (Magnetic nano-particle) dose (mg/cm3) that can induce the required therapeutic effects during magnetic nanoparticle hyperthermia (MNH). The investigation is done through the MNH simulations on the tumor models generated from DCE_MRI DICOM images of breast cancer from TCIA (‘The Cancer Imaging Archive’). Five tumor models are created from MRI data using 3D slicer software having size range of 3 cm3 to 15 cm3. The FEM-based solver (COMSOL multi-physics) is used to simulate bioheat transfer physics in all five extracted models. Single and multi-point injection strategies have been adopted to induce MNP in tumor tissues. The required MNP dose that may induce necessary therapeutic effects is evaluated by comparing the therapeutic effects produced by constant dose (CD) (5 mg/cm3) and variable reduced dose (RD) (5.5–2.8 mg/cm3) methodologies. Results show that for the requisite therapeutic effects, injected MNP doses (mg/cm3) should not remain constant as the size of the tumor increases. In fact, MNP dose (mg/cm3) should be reduced as the size of the tumor increases. Results also show that RD works better with a multi-injection strategy than a single injection of MNP. It has been found that the effective MNP dose (mg/cm3) is reduced by 50 % for the biggest tumor size (15 cm3) using multi-injection MNP delivery with respect to the smallest tumor (3 cm3) selected in this study.

Delivery of magnetic nanoparticles to lung cancer cells via polarized macrophages: A riveting tale of a bio-inspired phenomenon

Macrophages critically influences the tumor progression. The bio-carriers like macrophages have proven successful in circumventing this mammoth challenge by selectively infiltrating cancerous cells with anticancer drugs. Moreover, macrophage phenotypes have been found to have a key role in early phage of angiogenesis in the lungs. Phenotypic macrophages will serve to billet the iron, which has been found to have cancer cell-killing proficiency. Recent studies have shown the modulation of the molecular mechanism for tumor suppression by iron oxide (IO) nanoparticles. In addition, previous research focus on the interlink connections of iron and macrophages concerning macrophage polarization and consequent tumor suppression. However, we found that the initiation of the molecular response by external macrophages carrying anticancer agents has an exceptional breach in current drug delivery technology. We assume that macrophages carrying IO nanoparticles prepared by insemination-like formulation strategy to initiate the three-way response 1) directly invading the tumors with in vitro polarized macrophages; 2) Simultaneously delivering IO nanoparticles to augment the tumor suppression, and 3) IO deposition in TME further encourages polarization from M2 to proinflammatory M1 macrophages. Therefore, in the present study, we hypothesize that magnetic nanoparticles that are entrapped in phenotypic polarized macrophages will have striking potential to target lung cancer. In this hypothesis, we discussed the molecular interplay of iron and macrophages, in-vitro internalization of iron nanoparticles, and in vivo release inside the tumor cell.

Aggregation Volume Estimator–Based Offline Programming Guidance of Magnetic Nanoparticles in the Realistic Rat‐Brain Vasculature Model

Targeted delivery of magnetic nanoparticles (MNPs) to an area of a blood vessel with fluidic flow is hampered by the lack of a suitable real‐time imaging modality for MNPs, the control system complexity, and low targeting performance. Herein, an offline programming guidance (OLPG) scheme for aggregated MNPs is proposed based on a real‐time aggregation volume estimator. The proposed aggregation volume estimator based on a magnetic drug‐targeting simulator reflects volume changes of aggregated MNPs; hence, it can model a magnetic force acting on aggregated MNPs in real time while enhancing targeting performance. The proposed guidance system is evaluated using a simulation testbed and in vitro model of the rat brain, which yields comparable results at different fluid viscosities, flow velocities, target areas, and flow types. The OLPG with the aggregation volume estimator improves targeting performance by 116%–409% compared with the default mode, and by 111%–180% compared to the performance without the aggregation volume estimator. Furthermore, a guidance margin predicts enhanced targeting performance (root‐mean‐square error < 5%) irrespective of the flow environment. The proposed guidance strategy has the potential to overcome the problems caused by the lack of an imaging modality, control‐system complexity, and low targeting performance.

Transcranial application of magnetic pulses for improving brain drug delivery efficiency via intranasal injection of magnetic nanoparticles.

As the blood-brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP's transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.

Improvement of Targeted Therapy by E. coli Phage-lysate Vaccination: Tumor Microenvironment Modulation and Magnetic Nanoparticle Delivery Enhancement in Tumor Tissue

Improvement of Targeted Therapy by E. coli Phage-lysate Vaccination: Tumor Microenvironment Modulation and Magnetic Nanoparticle Delivery Enhancement in Tumor Tissue

Magnetic hyperthermia of AFe2O4 (A = Fe, Mn, Co) nanoparticles prepared by Co-precipitation method

With 10 million deaths in 2020 cancer remains one of the most challenging diseases in contemporary medicine. Chemotherapy, surgery, and radiation therapy are commonly used to treat tumors. These treatments harm healthy tissues and succeed rarely in advance stages of cancer. Recent studies indicate that magnetic hyperthermia, which involves targeted delivery of magnetic nanoparticles to tumor cells followed by localized remote heating of cancer tissues could revolutionize clinical practice in the treatment of cancer, either as standalone intervention or adjunct to radiotherapy and chemotherapy. Water dispersible magnetic nanoparticles (MNPs) of ferrites (AFe2O4; A = Fe, Mn, Co) are the promising candidates for magnetic hyperthermia due to their high chemical stability, biocompatibility, moderate magnetization and high specific absorption rates (SAR). In this article, we have evaluated magnetic hyperthermia efficiency of water based magnetic fluids of AFe2O4. AFe2O4 NPs were synthesized by chemical co-precipitation method. Nanoparticles were coated with a bilayer of oleic acid and dispersed in water. Structural and magnetic properties of MNPs were investigated by X-Ray diffraction (XRD) and vibrating sample magnetometer (VSM). XRD study revealed that AFe2O4 NPs exhibits cubic inverse spinel structure. Fe3O4 (Ms = 48 emu/g, Mr = 2.60 emu/g, Hc = 49 Oe), MnFe2O4 (Ms = 40 emu/g, Mr = 2.60 emu/g, Hc = 35 Oe) and CoFe2O4 (44 emu/g, Mr = 10.10 emu/g, Hc =440 Oe) NPs exhibits soft ferromagnetic behaviour. Magnetic hyperthermia measurements were performed as a function of magnetic field strength (2–10 mT), field frequency (162–935.6 kHz) for 10 minutes. MNPs exhibits highest SAR values for 10 mT field strength at 935.6 kHz. Amongst the tested MNPs, Fe3O4 possess the highest SAR value (27.35 W/g), followed by MnFe2O4 (1.91 W/g) and CoFe2O4 (0.94 W/g). Considering this, it is concluded that amongst the inverse spinel ferrites AFe2O4, Fe3O4 NPs and most suitable for magnetic hyperthermia applications.

Mathematical Optimisation of Magnetic Nanoparticle Diffusion in the Brain White Matter.

Magnetic nanoparticles (MNPs) are a promising drug delivery system to treat brain diseases, as the particle transport trajectory can be manipulated by an external magnetic field. However, due to the complex microstructure of brain tissues, particularly the arrangement of nerve fibres in the white matter (WM), how to achieve desired drug distribution patterns, e.g., uniform distribution, is largely unknown. In this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs, we conducted a pilot study to investigate the effects of key parameters in the MNP delivery on the particle diffusion behaviours in the brain WM microstructures. The results show that (i) a uniform distribution of MNPs can be achieved in anisotropic tissues by adjusting the particle size and magnetic field; (ii) particle size plays a key role in determining MNPs' diffusion behaviours. The magnitude of MNP equivalent diffusivity is reversely correlated to the particle size. The MNPs with a dimension greater than 90 nm cannot reach a uniform distribution in the brain WM even in an external magnitude field; (iii) axon tortuosity may lead to transversely anisotropic MNP transport in the brain WM; however, this effect can be mitigated by applying an external magnetic field perpendicular to the local axon track. This study not only advances understanding to answer the question of how to optimise MNP delivery, but also demonstrates the potential of mathematical modelling to help achieve desired drug distributions in biological tissues with a complex microstructure.

Optimal heat transport induced by magnetic nanoparticle delivery in vascularised tumours

We describe a novel mathematical model for blood flow, delivery of nanoparticles, and heat transport in vascularised tumour tissue. The model, which is derived via the asymptotic homogenisation technique, provides a link between the macroscale behaviour of the system and its underlying, tortuous micro-structure, as parametrised in Penta and Ambrosi (2015). It consists of a double Darcy’s law, coupled with a double advection–diffusion–reaction system describing heat transport, and an advection–diffusion–reaction equation for transport and adhesion of particles. Particles are assumed sufficiently large and do not extravasate to the tumour interstitial space but blood and heat can be exchanged between the two compartments. Numerical simulations of the model are performed using a finite element method to investigate cancer hyperthermia induced by the application of magnetic field applied to injected iron oxide nanoparticles. Since tumour microvasculature is more tortuous than that of healthy tissue and thus suboptimal in terms of fluid and drug transport, we study the influence of the vessels’ geometry on tumour temperature. Effective and safe hyperthermia treatment requires tumour temperature within certain target range, generally estimated between 42 °C and 46 °C, for a certain target duration, typically 0.5h to 2h. As temperature is difficult to measure in situ, we use our model to determine the ranges of tortuosity of the microvessels, magnetic intensity, injection time, wall shear stress rate, and concentration of nanoparticles required to achieve given target conditions.

Macrophage-mediated delivery of magnetic nanoparticles for enhanced magnetic resonance imaging and magnetothermal therapy of solid tumors

Magnetothermal therapy (MHT) has attracted significant attention due to the advantages of non-/minimal invasiveness, high efficiency, and excellent tissue penetration. However, developing small MHT agents (<50 nm) with excellent magnetothermal conversion performance and high tumor enrichment is a great challenge. Herein, a macrophage-mediated delivery of small Fe@Fe3O4-DHCA nanoparticles (∼14 nm) was designed for enhanced magnetic resonance imaging (MRI) and MHT of solid tumors. Based on the “Trojan horse” loading properties of the macrophages (RAW267.4 cells), the aggregation of Fe@Fe3O4-DHCA nanoparticles in the cells results in an enhanced MRI and magnetothermal performance in vitro. In addition, the MHT effect of RAW267.4 loaded with Fe@Fe3O4-DHCA in vivo is better than that of Fe@Fe3O4-DHCA alone, due to the tumor-targeting performance of RAW267.4 cells. This macrophage-mediated delivery provides a new strategy for the enhanced treatment effect of MHT based on Fe@Fe3O4-DHCA nanoparticles, and has great application potential for clinic tumor therapy.

Magnetic Nano-Sized SDF-1 Particles Show Promise for Application in Stem Cell-Based Repair of Damaged Tissues.

Stem cell-based therapy is a promising option for repair of injured tissue. Stem cells have homing characteristics and can be mobilized to the injury sites following activation, under the regulation of the SDF-1/CXCR4 axis. However, a sufficient level of stem cell aggregation and retention is essential for ensuring favorable repair outcomes. Problems related to stem cell delivery/recruitment efficiency and retention in the injury site are among the main challenges faced during in vivo studies on stem cell therapy. In this study, we designed an SDF-1(alpha) magnetic nanoparticle delivery system for stem cell recruitment. We expressed and purified a biotin-labeled SDF-1(alpha) protein and immobilized it on streptavidin-modified magnetic nanoparticles (MNP) through the streptavidin–biotin linkage, with an efficiency of approximately 14%. The physicochemical properties of the SDF-MNP in glycerol buffer were similar to those of the streptavidin-modified MNP. Further evidence suggested that SDF-MNP barely show cytotoxicity even at a concentration of 125 µg/ml MNP and have a promising chemotaxis effect on mesenchymal stem cells in vitro and in vivo. Our study provides a strategy for the assembly of magnetic nanoparticle carrier systems for protein factors, as well as preliminary evidence for the application of SDF-MNP in stem cell-based therapy for the regeneration of injured bone tissue.

Conjugation of Oligo-His Peptides to Magnetic γ-Fe2O3@SiO2 Core-Shell Nanoparticles Promotes Their Access to the Cytosol.

The endosomal entrapment of functional nanoparticles is a severe limitation to their use for biomedical applications. In the case of magnetic nanoparticles (MNPs), this entrapment leads to poor heating efficiency for magnetic hyperthermia and suppresses the possibility to manipulate them in the cytosol. Current strategies to limit their entrapment include functionalization with cell-penetrating peptides to promote translocation directly across the cell membrane or facilitate endosomal escape. However, these strategies suffer from the potential release of free peptides in the cell, and to the best of our knowledge, there is currently a lack of effective methods for the cytosolic delivery of MNPs after incubation with cells. Herein, we report the conjugation of fluorescently labeled cationic peptides to γ-Fe2O3@SiO2 core-shell nanoparticles by click chemistry to improve MNP access to the cytosol. We compare the effect of Arg9 and His4 peptides. On the one hand, Arg9 is a classical cell-penetrating peptide able to enter cells by direct translocation, and on the other hand, it has been demonstrated that sequences rich in histidine residues can promote endosomal escape, possibly by the proton sponge effect. The methodology developed here allows a high colocalization of the peptides and core-shell nanoparticles in cells and confirms that grafting peptides rich in histidine residues onto nanoparticles promotes NPs' access to the cytosol. Endosomal escape was confirmed by a calcein leakage assay and by ultrastructural analysis in transmission electron microscopy. No toxicity was observed for the peptide-nanoparticles conjugates. We also show that our conjugation strategy is compatible with the addition of multiple substrates and can thus be used for the delivery of cytoplasm-targeted therapeutics.

Simulation of magnetic nanoparticles crossing through a simplified blood-brain barrier model for Glioblastoma multiforme treatment

Background and ObjectivesGlioblastoma multiforme is considered as one of the most aggressive types of cancer, while various treatment techniques have been proposed. Magnetic nanoparticles (MNPs) loaded with drug and magnetically controlled and targeted to tissues affected by disease, is considered as a possible treatment. However, MNPs are difficult to penetrate the central nervous system and approach the unhealthy tissue, because of the blood-brain barrier (BBB). This study investigates numerically the delivery of magnetic nanoparticles through the barrier driven by normal pressure drop and external gradient magnetic fields, employing a simplified geometrical model, computational fluid dynamics and discrete element method. The goal of the study is to provide information regarding the permeability of the BBB under various conditions like the imposed forces and the shape of the domain, as a preliminary predictive tool. MethodsTo achieve that, the three-dimensional Navier-Stokes equations are solved in the margin of a blood vessel along with a discrete model for the MNPs with various acting forces. The numerical results are compared with experimental measurements showing that the model can predict acceptably the flow behavior. ResultsThe effect of nanoparticles’ size, external magnetic field and blood flow in the vessel, on the brain-barrier's permeability are investigated. Three different cases of available area among the endothelial cells per the MNPs’ size ratio are also examined, showing that the MNPs’ size and available area is not the dominant parameter affecting the permeability of the BBB. The results indicate that the applied magnetic field enhances the drug delivery into the central nervous system (CNS). When larger MNPs (∼100 nm) are exposed to an external magnetic field, the permeability can be improved up to 30%, while it is shown that smaller MNPs (∼10 nm) cannot be driven by the applied magnetic field and in this case the permeability remains relatively unchanged. Finally, the blood flow increase leads to a permeability improvement up to 15%. ConclusionsThe applied magnetic field improves up to 45% the permeability of the BBB for MNPs of 100 nm. The geometric characteristics of the endothelial cells, the nanoparticles’ size and the blood flow are not so decisive parameters for the drug delivery into the CNS, compared to the external magnetic force.

Controlling the Movement of Magnetic Iron Oxide Nanoparticles Intended for Targeted Delivery of Cytostatics.

BackgroundA promising approach to solve the problem of cytostatic toxicity is targeted drug transport using magnetic nanoparticles (MNPs).PurposeTo use calculation to determine the optimal characteristics of the magnetic field for controlling MNPs in the body, and to evaluate the efficiency of magnetically controlled delivery of MNPs in vitro and in vivo to a tumour site in mice.Material and MethodsFor the in vitro study, reference MNPs were used, while for in vivo studies, MNPs coated in polylactide including fluorescent indocyanine (MNPs-ICG) were used. The in vivo luminescence intensity study was performed in mice with tumours, with and without of a magnetic field at the sites of interest. The studies were performed on a hydrodynamic stand developed at the Institute of Experimental Medicine of the Almazov National Medical Research Centre of the Ministry of Health of Russia.ResultsThe use of neodymium magnets facilitated selective accumulation of MNPs. One minute after the administration of MNPs-ICG to mice with a tumour, MNPs-ICG predominantly accumulated in the liver, in the absence and presence of a magnetic field, which indicates its metabolic pathway. The intensity of the fluorescence in the animals’ livers did not change over time, although an increase in fluorescence in the tumour was observed in the presence of a magnetic field.ConclusionThis type of MNP, used in combination with a magnetic field of calculated strength, can form the basis for the development of magnetically controlled transport of cytostatic drugs into tumour tissue.

Enzymatic Delivery of Magnetic Nanoparticles into Mitochondria of Live Cells.

Delivering magnetic nanoparticles (MNPs) into mitochondria provide a facile approach to manipulate cell life because mitochondria play essential roles in cell survival and death. Here we report the use of enzyme-responsive peptide assemblies to deliver MNPs into mitochondria of live cells. The mitochondria-targeting peptide (Mito-Flag), as the substrate of enterokinase (ENTK), assembles with MNPs in solution. The MNPs that are encapsulated by Mito-Flag peptides selectively accumulate to the mitochondria of cancer cells, rather than normal cells. The mitochondrial localization of MNPs reduces the viability of the cancer cells, but hardly affects the survival of the normal cell. This work demonstrates a new and facile strategy to specifically transport MNPs to the mitochondria in cancer cells for exploring the applications of MNPs as the targeted drug for biomedicine and cancer therapy.