MAGNETIC NANOPARTICLES FOR THEIR THERAPEUTIC APPLICATIONS

MAGNETIC NANOPARTICLES FOR THEIR THERAPEUTIC APPLICATIONS

Divyani Singh * and Prashant Shukla

Department of Pharmaceutics, Hygia Institute of Pharmaceutical Education and Research Faizullahganj, Prabhandh Nagar, Lucknow, Uttar Pradesh, India.

ABSTRACT: Magnetic nanoparticles are hugely used in hyperthermia, targeted drug delivery processes, diagnosis, extraction, and cellular imaging of biological molecules, which can be widely used in cancer treatment. The focus of attention is on formation, features, types, made work, coating material, and therapeutic application of magnetic nanoparticles. It also pivots in safety and biocompatibility in magnetic nanoparticles (MNPs). Particles within the size range of nanoscale exhibit magnetic properties and are known as magnetic nanoparticles (MNPs). The major advantage of magnetic nanoparticles is the targeting at the specific site. Various polymerization and coating of metals can be done, such as applying chemotherapeutic drugs to correct inherited diseases. The various process of Magnetic Nanoparticles formation through diagrammatical picture is also discussed in this article. This review discusses the therapeutic application, preparation method, features of magnetic nanoparticles, types, made work, surface coating, biocompatibility, and safety.

Keywords: Restorative, Polymerization, Chemotherapeutic, Hyperthermia, Biocompatibility

INTRODUCTION: Nowadays, Magnetic nanoparticles (MNPs) have been investigated and researched by scientists and researchers ¹. Magnetic nanoparticles include an immense range of applications in various fields like environmental correction, magnetic resonance imaging (MRI), magnetically fluid in biomedicine and biotechnology and also in data base storage ². A magnetic nanoparticle in a 1-100 nm size range which is used and is appropriate in science and technology fields.

A magnetic nanoparticle (MNPs) contains distinctive property as the huge surface volume ratio, and the size dependency with its magnetic feature intensely change from its bulk material. Magnetic nanoparticles have been enormously used in catalysis, nerve stimulation, etc ^3-22. Magnetic nanoparticles perform finest when their dimension is below the critical value, around 10-20 nanometres, but it also depends upon the material. The tiny particles make the lump decrease the power of nanoparticles.

The application includes shielding methods to chemically stabilize the uncoated nanoparticles to protect it from decomposition at the time and after synthesis. The techniques include grafting or coating the nanoparticles using organic compounds like polymers and surfactants or applying the inorganic layer of carbon or silica etc. ²³.

Magnetic nanoparticles (MNPs) have the finest magnetic inclination, biodegradable, and contain a small size effect and reactive function groups ²⁴. These are different from other because it gives a reaction to the external magnetic field used in various disease diagnosis and treatment. MNPs are also used in-vivo medicinal methods ²⁵. Specifically characterized nano-size particles are hugely used in bio-labeling, catalysis, and biological separation.

In the case of the catalytic reaction of the liquid phase, the tiny magnetic nano-size particles coordinates’ quasi homogenous system, which includes an edge like high reactivity, high separation and huge scattering. This article includes preparation methods of magnetic nanoparticles will be discussed briefly. Also, the protective coating methods, features, application and advantage of magnetic nanoparticles will be discussed ²⁶.

FLOW CHART OF NANO-MEDICINE

Devising of Magnetic Nanoparticles (MNPs): Magnetically induced nanoparticles are formulated by the two main methods- top-down and bottom-up methods. The illustrative diagram of the 2 methods is given below.

FIG. 1: METHOD OF PREPARATION OF MAGNETIC NANOPARTICLES

The top-down method includes ball milling, lithography, thin film or bulk material broken down into nanometre or micrometer size.

The bottom-up methods include magnetic nanoparticles formed by nucleation and growth process. Examples of bottom-up methods are GPC and wet chemical technique, and Sol-Gel method.

Ball Milling Method: John Benjamin developed the ball milling method in 1970 and used it to prepare reduced-size powders ²⁷. The working mechanism of the ball milling method is proposed by Fecht et al. ²⁸.

Mechanical ball milling method is bifurcated into two types: High energy ball milling method ²⁹ and ordinary ball milling method ^30-31. The high-energy ball milling method uses the ball mill’s high energy to mechanically alloy the raw material and transform the raw material into nano-spinel type ferrite. The ordinary ball milling method mainly involves crushing iron oxide particles of huge size into very fine particles by force between the steel ball and the inner wall of the ball mill. The mechanical ball milling method is further bifurcated into dry and wet methods. The wet method is a very good option for getting crystal structure with high magnetization ³².

For the preparation of magnetic nanoparticles, there are three stages in ball milling method. The first stage includes deformations and dislocations of bulk material due to collision between ball and bulk materials. The second stage includes formation of small granules (nano size) due to accumulation, recombination, and rearrangement due to dislocation. The third stage includes granules orientation becoming random, and edges of bulk material are peeled off. In this way, the crystallized form of nanoparticles is obtained from bulk material ³³.

In a recent experiment, the year 2020, the high-energy ball milling method was used for carbon encapsulated magnetic nanoparticles synthesis. In this experiment, carbon-encapsulated magnetic nanoparticles were manufactured using a high-energy ball mill working at an angular velocity of 1200rpm and having 100ml hardened stainless steel milling tanks. Ethylene glycol is used to reduce resistance, and dopamine drugs in various concentrations were added to the tank. Milling was stopped every 6 hours, and samples were collected from the tank. The sample was washed several times with deionized water and absolute ethanol, centrifuged and dried at 333 K in the air. Result found from this experiment includes- in the XRD pattern analysis, carbon encapsulation was found amorphous. The TEM observation found the average diameter as 13nm, 9nm, 7nm, and 6nm, respectively, for all samples. In magnetism analysis, smaller particles were found to have higher magnetic anisotropy constant because of various surface effects, and it contains larger coercive forces ¹³⁰.

GPC Method: GPC is the bottom-up method in which particles are nucleated and grow to form magnetic nanoparticles. For many decades, scientists and researchers have tried hard to prepare magnetic nanoparticles using the gas-phase condensation (GPC) method. Granqvist and Buhrman prepared very fine nanoparticles using the GPC method in the year 1970s. Sputtering sources were not used, but instead, a thermal evaporation source was used. The particles were formed in the static, inert gas. But the size and crystallinity of the nanoparticles were uncontrollable.

Mainly two possible models are proposed for the growth of the magnetic nanoparticles prepared by the GPC system based on the overlap between the growth zone of magnetic nanoparticles and the plasma zone. In the first model, nucleation and growth of magnetic nanoparticles occur in the plasma region (also known as the hot region); in this, magnetic nanoparticles show good crystallinity being bigger. In the second model, the nucleation and growth zone of magnetic nanoparticles partially overlap within the plasma zone.

In this model, smaller-sized magnetic nanoparticles are obtained having poor crystallinity   ³⁴. The merit of this method is that particle size and crystallinity are well-controlled, but the yield of it is generally low when compared with ball milling method. A sputtering source was adopted in 1991 for the GPC method, which made this method more effective for preparing magnetic nanoparticles ³⁵. The nanoparticle's yield and target utilization rate can be enhanced when compared with the conventional planar targets. This can be done using a hollow tube cathode where three important factors for manufacturing were used. The first includes using sputtering pressure higher than a threshold pressure. The second includes the nucleation process to occur outside the tube target to separate nucleation and growth. The third includes setting extra plasma at the tube outlet targeting for better crystallinity of the nanoparticles ¹³¹.

Thermal Decomposition Method: For the preparation of magnetic nanoparticles, thermal decomposition is one of the simplest methods. The thermal decomposition method produces high-quality superparamagnetic magnetic nanoparticles ^36-37. Decomposition of the organometallic complex uses precursors like light, heat, or sound to prepare nanoparticles ³⁸. The disadvantage of the thermal decomposition method is that magnetite crystal size is difficult to adjust because the thermal decomposition temperature used to get decreased by the boiling temperature of any selected solvent. Solvent free thermal decomposition method can also be used to prepare magnetic nanoparticles in which the temperature and reaction time can easily be changed. Also, magnetic nanoparticles' particle size and crystallinity can be varied more efficiently ³⁹. Nowadays, the thermal decomposition of iron oleate complexes in the presence of oleic acid using a heating process is a much more convenient technique for producing large-scale nanoparticles ^40-41.

An example includes preparing high-quality ferrofluid-based magnetite particles made using the thermal decomposition method where PMAO acts as the novel-phase transfer ligands. PMAO enhances the ferrofluid stability for as long as 6 months. At the concentration of approx. 5 mg/ml, SAR values are higher as 66.04 W/g measured at magnetic field amplitude of 80 Oe and frequency around 178 kHz. Manufactured ferrofluid gives readily available and cost-effective cancer treatment and diagnosis methods for future use ¹³².

FIG. 2: EXAMPLE OF FORMATION OF HYDROPHILIC SPION IN AQUEOUS SOLVENT USING THERMAL DECOMPOSITION

Sol-Gel Method: The sol-gel method is a type of wet-chemical technique that is immensely used to prepare nanoparticles and thin films ^42-44. The use of polysiloxane layers with many functional groups (or a combination of them) has made it a way to use the sol-gel method in nanotechnology ⁴⁵. The sol-gel method contains various advantages over another, like it has good homogeneity, low cost, and is highly pure. The Sol-gel method is mainly used to prepare magnetic nanoparticles using metallorganic precursors ^46-47. Using the sol-gel method, ferric nitrate is reacted with ethylene glycol to produce iron oxides and a mixture of iron oxides. Still, pure magnetite cannot be produced using this method ⁴⁸. Magnetic nanoparticles can be easily synthesized using the sol-gel method combined with annealing under the vacuum using inexpensive, non-toxic ferric nitrate and ethylene glycol as initial materials. Magnetic nanoparticles can be obtained at a temperature range of at least 200-400 degrees Celsius. The size of obtained magnetic nanoparticles can be varied by varying annealing temperature, and magnetic properties can be easily evaluated ⁴⁹. In a recent experiment, a Mg0.5Zn0.5FenO4 magnetic nanoparticle, a novel catalyst, was efficiently synthesized using the green sol-gel process and worked as the magnetic photocatalyst for the fast decolorization of RB21 dye under encompassing conditions. This experiment is mainly performed to synthesize environmentally friendly, non-toxic, economical, easy to scale up, and free from volatile organic solvent, surfactants, etc. ¹³³.

FIG. 3: EXAMPLE OF FORMATION OF HYDROPHILIC SPION IN AQ. SOLUTION USING SOL-GEL METHOD

Co-Precipitation Method: Co-precipitation is very effective and convenient way to formulate iron oxide from aqueous Fe₂+/Fe₃+ salt solution with the help of addition of base under ideal atmosphere at room temperature or elevated temperature ⁵⁰. In the homogenous aqueous solution, the hydrothermal condition was usually used to obtain ferrite nanoparticles by the co-precipitation of Fe³⁺ and Co²⁺ ions in the alkaline aqueous solution ⁵¹. Rajendrain et al. demonstrated 6-20 nm sized cobalt ferrites prepared at room temperature in the aqueous solution by the oxidation of Fe³⁺ and Co²⁺ ions ⁵². The size and magnetic properties of cobalt ferrite nanoparticles formulated by the co-precipitation method can vary greatly and depend upon the pH, salt concentration, counterion nature and stirring speed, etc. No systematic study has been done to study the effect of precipitation temperature on the synthesis of CoFe₂O₃ in a homogeneous aqueous solution prepared by the co-precipitation method ⁵³. Co1-xZnxFe₂O₄ nanoparticles having different x values were synthesized by the co-precipitation method. This nanoparticle possesses a single-phase cubic spinel structure confirmed by the XRD analysis method. Crystallite size increases with increasing Zn replacement in prepared samples, which was eventually confirmed by XRD study ¹³⁴.

FIG. 4: EXAMPLE OF FORMATION OF HYDROPHILIC SPIONs

Microemulsion method and hydrothermal methods are also used to in the formation of magnetic nanoparticles. In the microemulsion method, a micro emulsion is thermodynamically stable isotropic dispersion of two immiscible liquids; the micro domain of both liquids is stabilized by interfacial film of surfactant molecule ⁵⁴. The hydrothermal method's hydrothermal synthesis system contains metal linoleate, ethanol-linoleic acid liquid phase, and water-ethanol solution at various reaction temperatures under hydrothermal conditions ⁵⁵.

TABLE 1: OUTLINE OF COMPARISON BETWEEN VARIOUS PREPARATIONS METHODS OF MNPs

TABLE 2: MERITS AND DEMERITS OF VARIOUS MANUFACTURING METHODS OF MNPs

Features Magnetic Nanoparticles: A physical and chemical features of magnetic nanoparticles mainly depends on their molecular composition, chemical structure, and synthesis route (preparation pathway). A magnetic nanoparticle shows superparamagnetic nature and ranges from 1 to 100 nm in size.

Surface Features:

Surface Charging: Veiseh et al. proposed that charged magnetic nanoparticles cause absorption of proteins into it, which is recognized by RES and removed from circulation (Duran, et al. 2008). A magnetic nanoparticle with a positive charge binds to non-specific cells, and magnetic nanoparticles with strong negative charge increase liver uptake.

This process gives an electric potential that provides the basis of electrophoresis, the movement of dispersed colloids relative to fluid on application of an external electric field. Duran et al. suggest examples of how this helps in the preparation and the use of nanoparticles, such as giving a coat and drug loading ⁵⁶.

Surface Effect: On decreasing particle size, many nanoparticle atoms are surface atoms that indicate that surface and interfacial tension are essential. For example, for face-cantered cubic (fcc) cobalt with a diameter of approximately 1.6 nm, 60% of total spins is surface spins ⁵⁷.

Size-dependent Magnetic Features: Magnetic nanoparticles exhibit very distinguished magnetic feature that differs from the bulk material. Features like coactivity (Hc) and susceptibility depend upon size, composition, and shape differences ⁵⁸. When the size of nanoparticles is reduced below the critical value (DC), individual nanoparticles become a single magnetic domain and exhibit superparamagnetic behaviour when the temperature is adjusted above the blocking temperature (Tb). These nanoparticles have a larger constant magnetic moment and exhibit gigantic paramagnetic atoms with a higher response speed when magnetic fields are applied with zero remanences (residual magnetism) and coactivity (the field required to bring magnetization ⁸⁴ to zero). These properties make superparamagnetic nanoparticles very forceful against the magnetic resonance contrast agents. Another size-dependent feature of magnetic nanoparticles is super-paramagnetism. Magnetic anisotropic energy resists from spin-up form to spin-down form of magnet which is proportional to multiplication of magnetic anisotropic constant(Ku) and volume of magnet (V) ¹³⁵. Bulk materials have anisotropic magnetic energies, which are much higher than thermal energies (kT); the thermal energy of nanoparticles inverts the magnetic spin direction, following magnetic fluctuation results in total zero magnetization, called superparamagnetism ¹³⁶.

Types of Magnetic Nanoparticles:

Oxides:

Ferrite: Ferrite nanoparticles are so much researched magnetic nanoparticles till now. When the ferrite nanoparticles get less than 128 nm, they become superparamagnetic, preventing self-lumps as they display magnetic behaviour on an external magnetic field application. The remanence becomes zero when the external magnetic field is removed. Like the non-magnetic oxide nanoparticles, the surface of ferrite nanoparticles is often altered by silicones or phosphoric acid derivatives, surfactants, etc., to increase its stability in the solution.

Metallic Magnetic Nanoparticles: Metallic core of magnetic nanoparticles can be modified by surfactants, oxidation, precious metals, and oxidation. In the presence of oxygen, Co nanoparticles forms anti-ferromagnetism, CoO layer on Co nanoparticle’s surface ⁵⁹. Nowadays, work has been done on producing Co core Co O shell nanoparticles with golden outer shells. Nanoparticles having a magnetic core made of basic iron or cobalt with a non-reactive shell made of grapheme is being synthesized recently. It consists of various merits as compared with ferrite or elemental nanoparticles like:

Higher stability in an organic solvent as well as in the acidic and basic medium. The chemistry of graphene surfaces uses many methods already known for carbon nanotubes. Higher magnetization.

Functionalization and Surface Coating of MNPs:

Polymeric Coatings: For biomedical applications, surface coating is essential for magnetic nanoparticles. Because of the superparamagnetic properties, nanoparticles are still inclined to form a lump due to their high surface energy. Colloidal electrostatic stabilization formed due to the repulsion of surface charges on nanoparticles is not correct to prevent lumps in biological fluids because salts or other electrolytes can neutralize this charge. Also, the evading uptake by RES and maintaining a lengthy plasma half-life is crucial for many MNPs application in medicine ⁶⁰.

To prevent formation of lumps and opsonisation, the polymeric coating is done over nanoparticles which gives a steric barrier to nanoparticles. Also, these coating provides surface charge and chemical functionality to the nanoparticles. Due to coating, some variation occurs in the nature of the chemical structure of the polymer (ex-hydrophilic/hydrophobic, biodegradability etc), length or molecular weight of polymer, and manner in which polymer is attached (ex-electrostatic or covalent bonding), the conformation of the polymer and amount of surface covered. Monomeric species like biophosphonates ⁶¹, dimercaptosuccinic acid (DMSA) ⁶² and alkoxysilanes ^63-64 are checked and its coating on magnetic nanoparticles.

Liposome and Micelles: Liposome drug delivery carrier is one of the oldest forms of nanomedicine. Liposomes are the phospholipids bilayered membrane carrier system ranging from 100 nm to 5 micrometers in size and are used in the delivery of proteins, peptides, small molecules, DNA, and MR imaging contrast agents ⁶⁵.

The merit of liposomal encapsulation is its in-vivo nature and also to determine PEGylation processes, which gives wider circulation times. Liposomes can also encapsulate a larger number of magnetic nanoparticles core and deliver all at a time, avoiding dilution at the targeted site. Combining therapeutic agents in payloads enhances the multifunctionality of the vehicles. Multifunctional micelles forms amphiphilic block copolymer that entrapped magnetic nanoparticles for various applications ^66-67. Martine et al. formulate magnetic-loaded liposome (MFLs) by encapsulating maghemite nanocrystal within unilamellar vesicles of phosphatidylcholine and DSPE-PEG₂₀₀₀ ⁶⁸.

Core-shell Structures: Core-shell structures use biocompatible silica or gold to encapsulate the magnetic nanoparticles, which is very much used for developing MRI contrast agents or MTCs for drug delivery. MRI is free from radiation technique which is used to study clinical-based diagnosis ¹⁰². The non-reactive coating protects against chemical degradation of magnetic core and prevents the release of potentially toxic chemicals. Specialization chemistry is generally established between these materials and those made of magnetic nanoparticles.

Silica shells are a very beneficial option to be used as protective coating on magnetic nanoparticles due to its stability within aqueous conditions and easy synthesis. The sol-gel process uses tetraethoxysilane (TEOS) to produce a coating of measured thickness ^69-70. Using functional groups like alkoxysilanes, 3-aminopropyltriethyoxysilane (APS) allows for reactive surface groups, which should add to core-shell structures. Also, the potential to encapsulate functional molecules like changing images or therapeutic agents within the protective matrix is unique property and potential to these nanostructures ^71-72.

Functional Ligands: Ligands like the targeting agents, permeation enhancers, optical dyes, and the therapeutic agent’s conjugate on the surface or incorporates within nanostructures. To perform nanoscale engineering, bio-conjugation chemistries utilized for protein coupling have been studied ^73-74.

Actions like avidin-biotin binding, use of heterobifunctional linkers from amide, ester, or disulfide bonds, and click chemistry ^75-76 are the latest and exhibit are attaching ligands to magnetic nanoparticles. Those using magnetic nanoparticles may find it helpful to view the basic concept of colloidal science to prevent unwanted flocculation or lumping during the processes ⁷⁷.

Biocompatibility and Safety of Magnetic Nanoparticles: Toxicity is a very serious problem and an important factor in regenerative medicine and tissue engineering.

MNPs in regenerative medicine needs the labelling of cells that are implanted within the body. Using particle which is toxic can significantly diminish the therapeutic efficacy of cell-based therapy. Toxicology studies the adverse effects of chemical, physical and biological agents on people, animals, and the environment. When MNPs are incorporated into therapy and transplanted within the body, the risk of MNPs accumulating inside the organ is a major problem. This could cause an immunological or inflammatory response by the body. The above are hugely undesired scenarios.

Applications: A huge type of application is present for this type of particle which mainly includes:

Medical Diagnosis and Treatments: Cancer can also be treated by attaching magnetic nanoparticles to free-floating cancer cells, capturing and carrying them out of the body. Magnetic nanoparticles are used in experimental cancer treatment called magnetic hyperthermia, where the heat of MNPs is used when they are placed in a different magnetic field. Magnetic nanoparticles are coated using antibodies targeting cancer cells or proteins. For the detection of cancer also, magnetic nanoparticles are used.

In-vivo Applications: For the in-vivo studies, two major factors are very important including:

Size and Surface Functionality: Particles with a diameter of 10-40 nm including ultra-small SPIOs play an essential role in prolonging blood circulation. Superparamagnetic iron oxide nanoparticles (SPIOs) diameter affects the in-vivo distribution without targeting surface ligands ⁷⁸.

Therapeutic Application:

Hyperthermia: When placing super para magnetic iron oxide in altering current (ac), magnetic field randomly changes the magnetization direction between parallel and anti parallel orientation, helps to transfer heating magnetic energy to particle. This property is used in vivo to increase temperature of tumour tissues to destroy pathological cells by hyperthermia. In the past studies, magnetic cationic liposomal nanoparticles and dextran-coated magnetite increases the temperature of tumour cell very effectively for hyperthermia treatment in cell irradiation.

Diagnostic Applications:

NMR Imaging: The formation of NMR imaging technique created a new class of pharmaceuticals called magneto-pharmaceuticals. When administered to patients, these drugs enhance the image contrast between normal and diseased tissue and tell the organ function status and blood flow. Also, it can be used to develop the new imaging method ⁸⁵. The combination of magnetic particles with florescent dyes or both is used, and radioactive tracers etc are under investigation ⁸⁶.

Genetic Engineering: Magnetic nanoparticles are used in various types of genetic applications. It is used for the separation/isolation of messenger RNA. It can be quickly done within 15 min. Magnetic bead is attached to a poly T tail. When mixed with mRNA, the poly-A tail of mRNA is attached to bead’s poly T tail, and separation occurs at the side of the tube and the liquid is poured out.

Industrial Applications: Magnetic encapsulation is very important in many areas of life and also in different branches of industry. Magnetic iron oxides and metallic iron ⁸³ are very commonly used as a man-made pigments in ceramics, paints, and porcelain. These materials are useful for the fundamental study of material science and its application also ⁷⁹.

TABLE 3: APPLICATIONS OF MNPs

TABLE 4: CLINICAL STUDIES OF MAGNETIC NANOPARTICLES

FIG. 5: MAGNETIC NANOPARTICLES ENCAPSULATION USING LAYER-BY-LAYER METHOD {MODIFIED FROM 103

FIG. 6: VARIOUS USES OF MAGNETIC NANOPARTICLES {MODIFIED FROM ¹⁰⁴

TABLE 5: LIST OF RECENT PATENTS FOR PREPARATION METHOD OF LIPID-BASED MAGNETIC NANOPARTICLES

CONCLUSION: Rapid development in the preparation of magnetic particles has allowed the use of new chemicals and compounds for more efficient targeting of the drug molecules to the targeted site, and many novel techniques are developing for applying a magnetic field, which can be used to treat a disease like cystic fibrosis and localized cancerous tumors. Very less clinical trials are done regarding magnetic nanoparticles, but their results are promising. Magnetic targeting is not useful in all cases but is still an effective tool as a biomedicine ⁸² used to treat different types of diseases and conditions.

ACKNOWLEDGEMENT: I am very grateful to the institute and the department for their support. I also express my gratitude to the official and another staff member of the Hygia Institute of Pharmaceutical Education and Research.

CONFLICTS OF INTEREST: There is no conflict of interest.

REFERENCE:

1. Ansari Mohammad Javed, et al: Synthesis and Stability of Magnetic Nanoparticles, Bio Nano Sci 2022; 12: 627-638.
2. Tran Hung-Vu: Multifunctional Iron Oxide Magnetic Nanoparticles for Biomedical Applications: A Review, Materials 2022; 15(2): 503.
3. Rojas Guadalupe Gabriel Flores: Magnetic Nanoparticles for Medical Applications: Updated Review, Macromol 2022; 2(3): 374-390.
4. Hillion Arnaud: Real-Time Observation and Analysis of Magnetomechanical Actuation of Magnetic Nanoparticles in Cells, Nano Lett 2022; 22(5): 1986-1991.
5. Obireddy Sreekanth Reddy: ROS-Generating Amine-Functionalized Magnetic Nanoparticles Coupled with Carboxymethyl Chitosan for pH-Responsive Release of Doxorubicin. Int J Nanomedicine 2022; 17: 589-601.
6. Er Elif Ozturk: Magnetic Nanoparticles Based Solid Phase Extraction Methods for the Determination of Trace Elements, Critical Review in Analytical Chemistry 2022, 52(2): 231-249.
7. Bhattacharya Soumya: Targeting Magnetic Nanoparticles in Physiologically Mimicking Tissue Microenvironment, ACS Applied Material Interfaces 2022; 14(28): 31689-31701.
8. Cetin Kemal: Magnetic nanoparticles embedded microcryogels for bilirubin Removal 2022; 112: 203-208.
9. Jia Y, Peng Y, Bai J, Zhang X, Cui Y, Ning B, Cui J and Gao Z: Magnetic nanoparticle enhanced surface plasmon resonance sensor for estradiol analysis Sensors Actuators B, Journal of Pharmaceutical Analysis 2018; 254: 629–35.
10. Sun Y, Fang L, Wan Y and Gu Z: Pathogenic detection and phenotype using magnetic nanoparticle-urease nanosensor Sensors Actuators B, Journal of Pharmaceutical Analysis 2018; 259: 428–32.
11. Hu Y, Ma W, Tao M, Zhang X, Wang X, Wang X and Chen L: Decorated‐magnetic‐nanoparticle‐supported bromine as a recyclable catalyst for the oxidation of sulphides. J Appl Polym Sci 2019; 135(34): 502003.
12. Moghaddam FM, Saberi V, Kalhor S and Veisi N: Palladium (II) Immobilized onto the glucose functionalized magnetic nanoparticle as a new and efficient catalyst for the one‐pot synthesis of benzoxazoles, Appl. Organometallic Chem 2018, 32: 4240.
13. Kuwahata A, Kaneko M, Chikaki S, Kusakabe M and Sekino M: Development of device for quantifying magnetic nanoparticle tracers accumulating in sentinel lymph nodes. AIP Adv 2018; 8: 56713.
14. Leshuk T, Holmes A, Ranatunga D, Chen P Z, Jiang Y and Gu F: Magnetic flocculation for nanoparticle separation and catalyst recycling Environ Sci Nano 2018; 5: 509–519.
15. Tay AKP: Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels. Cham Spr 2018; 83–93.
16. Jasemi Amir: A porous calcium-zirconia scaffolds composed of magnetic nanoparticles for bone cancer treatment: Fabrication, characterization and FEM analysis. Ceramics International 2022; 48(1): 1314-1325.
17. Xu Jiaxin: β-Cyclodextrin functionalized magnetic nanoparticles for the removal of pharmaceutical residues in drinking water, Journal of Industrial and Engineering Chemistry 2022; 109: 461-474.
18. AbouSeada Nour: Synthesis and characterization of novel magnetic nanoparticles for photocatalytic degradation of indigo carmine dye. Material Science for Energy Technologies 2022; 5: 116-124.
19. Zhang Xindan: Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers, ACS Applied Material Interfaces 2022; 14(28): 31677-31688.
20. Azeez Rana Abbas: Biosorption of dye by immobilized yeast cells on the surface of magnetic nanoparticles, Alexandria Engineering Journal 2022; 61(7): 5213-5222.
21. Bica loan: Composite Materials Based on Polymeric Fibers Doped with Magnetic Nanoparticles: Synthesis, Properties and Applications, Nanomat 2022; 12(13): 2240.
22. Hua Yanglong, Yu Jing and Gao Song: Chapter 9 Magnetic Nanoparticle-based Cancer Therapy, Synthesis and biomedical applications of magnetic nanomaterials 2022: 261-290.
23. Gaete Jose: Mechanistic Insights into the Thermal Decomposition of Ammonium Perchlorate: The Role of Amino-Functionalized Magnetic Nanoparticles, ACS Applied Material Interfaces 2022; 61(3): 1447-1455.
24. Vidovix Taynara Basso: Investigation of two new low-cost adsorbents functionalized with magnetic nanoparticles for the efficient removal of triclosan and a synthetic mixture, Environmental Science and Pollution Research 2022; 29: 46813-46829.
25. Allafchian Alireza, Hosseini Seyed Sajjad: Antibacterial magnetic nanoparticles for therapeutics: a review, The Institution of Engineering and Technology 2019; 13(8): 786-799.
26. Onishi Tatsuya: Application of Magnetic Nanoparticles for Rapid Detection and In Situ Diagnosis in Clinical Oncology, Cancers 2022; 14(2): 364.
27. Qureshi Albar Ali: Systematic Investigation of Structural, Morphological, Thermal, Optoelectronic and Magnetic Properties of High-Purity Hematite/Magnetite Nanoparticles for Optoelectronics, Nanomaterials 2022; 12(10): 1635.
28. Chen Yujing: Low-Temperature-Graphitized and Interpenetrating Network C/Fe3O4 Magnetic Nanocomposites with Enhanced Tribological Properties under High Temperature, ACS Applied Materials and Interfaces 2022; 14(29): 33922-33932.
29. Akramov DF: Effect of Milling on the Magnetic Properties of the Fe7S8 and Fe7Se8 Compounds, Physics of Metals and Metallography 2022; 123: 282-289.
30. Zhang Lianzhi: The Influence of Rotational Speed on Bonding Strength, Magnetic Properties, and Mechanical Properties of Fe3O4/ZrO2 Magnetic Composites, Journal of Materials Engineering and Performance 2022; 31: 1818-1827.
31. Zivotsky Ondrej: Structural and Magnetic Properties of Inverse-Heusler Mn2FeSi Alloy Powder Prepared by Ball Milling, Materials 2022; 15(3): 697.
32. Velásquez AA, Marín CC and Urquijo JP: Synthesis and characterization of magnetite-maghemite nanoparticles obtained by the high-energy ball milling method, Journal of Nanoparticle Research 2018; 20(3): 1400.
33. Kedzierska Magdalena: The Synthesis Methodology and Characterization of Nanogold-Coated Fe3O4 Magnetic Nanoparticles, Materials 2022; 15(9): 3383.
34. Chauhan Shraddha: Chapter 22 - Nanomaterials in biomedicine: Synthesis and applications, Advances in Nanotechnology-Based Drug Delivery Systems 2022; 585-604.
35. Schneider Joel R: Understanding and Utilizing Reactive Oxygen Reservoirs in Atomic Layer Deposition of Metal Oxides with Ozone, Chem. Mater 2022; 34(12): 5584-5597.
36. Ried JC: Design of concentrated colloidal dispersions of iron oxide nanoparticles in ionic liquids: Structure and thermal stability from 25 to 200 °C, Journal of Colloid and Interface Science 2022; 607(1): 584-594.
37. Torres Moises Bustamante, et al: Polymeric Composite of Magnetite Iron Oxide Nanoparticles and Their Application in Biomedicine: A Review, Polymers 2022; 14(4): 752.
38. Karami Mohammad Hossein: Thermal degradation kinetics of epoxy resin modified with elastomeric nanoparticles. Advanced Composites and Hybrid Materials 2022; 5: 390-401.
39. Pereir LG: Comparison of biofuel life-cycle GHG emissions assessment tools: the case studies of ethanol produced from sugarcane, corn, and wheat. Renew. Sust. Energy 2019; 110: 1-12.
40. Solgi Mehri: Synthesis of magnetic nanoparticles Fe3O4@CQD@Si(OEt)(CH2)3@melamine@TC@Ni(NO3) with application in the synthesis of 2-amino-3-cyanopyridine and pyrano[2,3-c]pyrazole derivatives, Research on Chemical Intermediates 2022, 48: 2443-2468.
41. Caldera Fabrizio: Magnetic Composites of Dextrin-Based Carbonate Nanosponges and Iron Oxide Nanoparticles with Potential Application in Targeted Drug Delivery. Nanomaterials 2022; 12(5): 754.
42. Kumar Nishant: Tuning in structural, optoelectronic, magnetic and ferroelectric properties of NiFe2O4 ceramics engineering nanomaterials by substitution of rare earth element, Pr3+ prepared by sol–gel method. Journal of Material Science: Materials in Electronics 2022; 33: 6131-6149.
43. Kushwaha Pratishtha, Chauhan Pratima: Influence of annealing temperature on microstructural and magnetic properties of Fe2O3 nanoparticles synthesized via sol-gel method, Inorganic and Nano-Metal Chemistry 2022; 52(7): 937-950.
44. Sharon VS: Superparamagnetic Nickel Ferrite Nanoparticles Doped with Zinc by Modified Sol–gel Method. Journal of Superconductivity and Novel Magnetism 2022; 35: 795-804.
45. Wang Jialing: Structural and magnetic properties of Ce3+doped Mg-Co ferrite prepared by sol–gel method, Journal of Material Science: Materials in Electronics 2022; 33: 11881-11895.
46. Chambers Matthew S: In Situ and Ex Situ X-ray Diffraction and Small-Angle X-ray Scattering Investigations of the Sol–Gel Synthesis of Fe3N and Fe3C, Inorg Chem 2022; 61(18): 6742-6749.
47. Subash M: Synthesis, characterizations of pure and Co2+ doped iron oxide nanoparticles for magnetic applications, Materials today: Proceedings 2022; 56(6): 3413-3417.
48. Farbod Mansoor: Optimization of sol–gel synthesis condition of Y2BaCuO5 nanoparticles using Taguchi robust design method and investigation of its magnetic behaviour, J of the Austral Cera Society 2022; 58: 549-55.
49. Guo Yuheng: Study on the Structure, Magnetic Properties and Mechanism of Zn-Doped Yttrium Iron Garnet Nanomaterial Prepared by the Sol-gel Method, Gels 2022; 8(5): 325.
50. Heydaryan Kamran: Tuning specific loss power of CoFe2O4 nanoparticles by changing surfactant concentration in a combined co-precipitation and thermal decomposition method, Ceramics International 2022; 48(12): 16967-16976.
51. Lin Chia-chang: A high-productivity process for mass-producing Fe3O4 nanoparticles by co-precipitation in a rotating packed bed. Powder Technol 2022; 395: 369-376.
52. Kumar Mukesh: Studies on the heating ability by varying the size of fe3o4 magnetic nanoparticles for hyperthermia, nanoscience and technology. An International Journal 2022; 13(3): 33-45.
53. JCPDS data base 22-1086.
54. Duodu G. Amo: Synthesis and characterization of magnetic nanoparticles: Biocatalytic effects on wastewater treatment, Materials today: Proceedin 2022; 62(1): 579-84.
55. Prill Busra, Yusan Sabriye: Synthesis and characterization of magnetic nanoparticles functionalized with different starch types, Particulate Science and Technology 2022; 40(5): 521-530.
56. Sun Nana: Study on the Coupling Effect of Microwave and Magnetic Nanoparticles on Oil Droplet Coalescence, SPE Journal 2022: 1-12.
57. Acevedo Pelayo Garcia: Significant Surface Spin Effects and Exchange Bias in Iron Oxide-Based Hollow Magnetic Nanoparticles, Nanomaterials 2022; 12(3): 456.
58. Pawlik Piotr: Application of iron-based magnetic nanoparticles stabilized with triethanolammonium oleate for Theranostics, Journal of Materials Science 2022; 57: 4716-4737.
59. Quresi Zubair Akbar: Triadic Hybridized Magnetic Nanoparticles Suspended in Liquid Streamed in Coaxially Swirled Disks, Nanomaterials 2022; 12(4): 671.
60. Osman Husaeyn: Synthesis of Polymer-Coated Magnetic Nanoparticles to the Surface of Activated Carbon and Kinetic Studies, NanoEra 2021; 1(2): 45-53.
61. Kheilkordi Zohreh: Recent advances in the application of magnetic bio-polymers as catalysts in multicomponent reactions, RSC Adv 2022; 12: 12672-12701.
62. Daya Radha, et al: Angiogenic Hyaluronic Acid Hydrogels with Curcumin-Coated Magnetic Nanoparticles for Tissue Repair, ACS Applied Materials and Inferences 2022; 14(9): 11051-11067.
63. Carothers Kyle J: Polymer-Coated Magnetic Nanoparticles as Ultrahigh Verdet Constant Materials: Correlation of Nanoparticle Size with Magnetic and Magneto-Optical Properties, Chemistry of Materials 2021; 33(13): 5010-5020.
64. Labbafzadeh Minoush Rahim: Application of magnetic electrospun polyvinyl alcohol/collagen nanofibres for drug delivery systems, Molecular Simulation 2018; 1-7.
65. Salkho Najla M: Photo-Induced Drug Release from Polymeric Micelles and Liposomes: Phototriggering Mechanisms in Drug Delivery Systems, Polymers 2022; 14(7): 1286.
66. Puzari Minakshi and Chetia Pankaj: Chapter 15- Nanotechnology-based cancer drug delivery. Advances in Nanotechnology Based Drug Deliv System 2022; 415-422.
67. Campora Simona and Ghersi Giulio: Recent developments and applications of smart nanoparticles in biomedicine, Nanotechnology 2022; 11(1): 2595-2631.
68. Koksharov Yu. A: Magnetic Nanoparticles in Medicine: Progress, Problems, and Advances. J of Communications Technology and Electronics 2022; 67: 101-116.
69. Nodehi R: Fe3O4@NiO core–shell magnetic nanoparticle for highly efficient removal of Alizarin red S anionic dye, International Journal of Environmental Science and Technology 2022; 19: 2899-2912.
70. Dadashi Jaber: Fabrication of Copper(II)-Coated Magnetic Core-Shell Nanoparticles Fe3O4@SiO2: An Effective and Recoverable Catalyst for Reduction/Degradation of Environmental Pollutants, Crystals 2022; 12(6): 862.
71. Hussain Manzoor: Fabrication of a Double Core–Shell Particle-Based Magnetic Nanocomposite for Effective Adsorption-Controlled Release of Drugs. Polymers 2022; 14(13): 2681.
72. Gabal MA: Synthesis, Structural, Magnetic and High-Frequency Electrical Properties of Mn0.8Zn0.2Fe2O4/Polypyrrole Core–Shell Composite Using Waste Batteries. Journal of Inorganic and Organometallic Polymers and Materials 2022; 32: 1975-1987.
73. Yu Xi: Design, Preparation, and Application of Magnetic Nanoparticles for Food Safety Analysis: A Review of Recent Advances. J Agric Food Chem 2022; 70(1): 46-62.
74. Liu Xubo: Manipulating Dispersions of Magnetic Nanoparticles, Nano Lett 2021; 21(7): 2699-2708.
75. Acidereli Hilal: Chapter 8- Magnetic nanoparticles: Nanoscale Processing 2021; 197-236.
76. Abdolrahimi Maryam: Magnetism of Nanoparticles: Effect of the Organic Coating, Nanomaterials 2021; 11(7): 1787.
77. Craciunescu Izabell: High-Performance Functionalized Magnetic Nanoparticles with Tailored Sizes and Shapes for Localized Hyperthermia Applications. J Phys Chem C 2021; 125(20): 11132-11146.
78. Huang Pin-Chieh: Biomechanical sensing of in vivo magnetic nanoparticle hyperthermia-treated melanoma using magnetomotive optical coherence elastography, Theranostics 2021; 11(12): 5620-5633.
79. Noor M. H. Mohamed: Assessing the effectiveness of magnetic nanoparticles coagulation/flocculation in water treatment: a systematic literature review. International J of Enviro Science and Technology 2022; 19: 6935-6956.
80. Alromi Dalal A: Emerging Application of Magnetic Nanoparticles for Diagnosis and Treatment of Cancer, Polymers 2021; 13(23): 4146.
81. Serio Francesca: Co-loading of doxorubicin and iron oxide nanocubes in polycaprolactone fibers for combining Magneto-Thermal and chemotherapeutic effects on cancer cells, J of Colloid and Interf Science 2022; 607(1): 34-44.
82. Golovin Yuri I: Non-Heating Alternating Magnetic Field Nanomechanical Stimulation of Biomolecule Structures via Magnetic Nanoparticles as the Basis for Future Low-Toxic Biomedical Applications, Nanomaterials 2021; 11(9): 2255.
83. Kidibule Peter E: Production and characterization of chitooligosaccharides by the fungal chitinase Chit42 immobilized on magnetic nanoparticles and chitosan beads: selectivity, specificity and improved operational utility, RSC Adv 2021; 11:5529-5536.
84. Lacovita C: Imaging Large Iron-Oxide Nanoparticle Clusters by Field-Dependent Magnetic Force Microscopy, The J of Physical Chem C 2021; 125(43): 24001-24010.
85. Kush Preeti: Aspects of high-performance and bio-acceptable magnetic nanoparticles for biomedical application, Asian J of Pharma Scie 2021; 16(6): 704-737.
86. Li Xuexin: Magnetic nanoparticles for cancer theranostics: Advances and prospects. Journal of Controlled Release 2021; 335: 437-448.
87. Khodaei A: Controlled temperature-mediated curcumin release from magneto-thermal nanocarriers to kill bone tumors, Bioactive Materials 2022; 11: 107-117.
88. Yankeelov TE: Quantitative multimodality imaging in cancer research and therapy. Nat Rev Clin Oncol 2016; 11: 670–680.
89. Yankeelov TE: Quantitative multimodality imaging in cancer research and therapy. Nat Rev Clin Oncol 2016; 11: 670–680.
90. Anselmo AC and Mitragotri S: A review of clinical translation of inorganic nanoparticles. AAPS J 2015; 17: 1041–1054.
91. Anselmo AC and Mitragotri S: Nanoparticles in the clinic. Bioeng. Transl Med 2016; 1: 10–29.
92. Mulvaney P: Standardizing nanomaterials, ACS Nano 2016; 10: 9763–9764.
93. Singh N: Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION), Nano Rev 2010; 1: 5358.
94. Stodt Malte FB: Phase-selective laser–induced breakdown spectroscopy in flame spray pyrolysis for iron oxide nanoparticle synthesis, Proceedings of the Combustion Institute 2021; 38(1): 1711-1718.
95. Zhang Zhongliang and Wen Gehui: “Synthesis and characterization of carbon-encapsulated magnetite, martensite and iron nanoparticles by high-energy ball milling method”, published in Materials Characterization 2020; 110502: 1-17.
96. Liu Jinming: “High-Yield Gas-Phase Condensation Synthesis of Nanoparticles to Enable a Wide Array of Applications” published by ACS applied nano materials, August 3 2020; 1-8.
97. Vuong Thi Kim Oanh: “PMAO-assisted thermal decomposition synthesis of high-stability ferrofluid based on magnetite nanoparticles for hyperthermia and MRI applications”, published by materials chemistry and physics 2020 122762: 1-8.
98. Moradnia Farzaneh: “Magnetic Mg0.5Zn0.5FeMnO4 nanoparticles: Green sol-gel synthesis, characterization, and photocatalytic applications”, published in Journal of Cleaner Production, Received 11 April 2020, Received in revised form 12 December 2020; 1-13.
99. Andhare Deepali D: “Effect of Zn doping on structural, magnetic and optical properties of cobalt ferrite nanoparticles synthesized via. Co-precipitation method”, published by Physica B: Physics of Condensed Matter, 583 2022; 412051: 1-6.
100. Fatima Hira: Fundamentals to Apply Magnetic Nanoparticles for Hyperthermia Therapy, Nanomaterials 2021; 11(5): 1203.
101. Wook Jun Young: “Nanoscaling Laws of Magnetic Nanoparticles and Their Applicabilities in Biomedical Sciences”, published by Department of Chemistry, Yonsei University, Seoul 120-749, Korea, 179-189.
     

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     How to cite this article:

     Singh D and Shukla P: Magnetic nanoparticles for its therapeutic applications. Int J Pharm Sci & Res 2023; 14(4): 1547-60. doi: 10.13040/IJPSR.0975-8232.14(4).1547-60.

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