See also antibodies as drug targetting agents
Introduction:
Magnetic nanoscale particles are of particular interest with respect to nanoparticles due to their magnetic properties. These nanoparticles ave been used to deliver theapeutic molecules, magnetic separation techniques and for use as contrast agents in NMR diagnosis.
The concept of using magnetic particles such as a ferromagnetic or a ferrimagnetic material into a patient’s body which is susceptible to the attractive effects of magnetic fields is not knew. Brown (US2003/0105382A1) for example disclsoes incorporating such a material into a patient and using a pulsed magnetic field from a device outside the patient’s body to induce motion in the magentic particles so as to break up thrombi and other masses or to enhance the action of lysing agents.
Volkonsky (US6,482,436) also teaches using a magnetically responsive composition which may carry biologically active substances. The composition/carrier is injected into the blood and a magnetic field which has been previously established exterior to the body at a preferred targetting site so as to guide the carrier to a targetting site.
Stetter (DE102005030986) also teches rotation of magnetic beads using superimposed magnetic alternating fields for enzymatic destruction of thrombi or remmoving artheriosclerotic deposits. Stetter teaches that the nanobeads can be coated with thrombolytic enzymes such as streptokinase which allows the enzymes to interact better with fibrin and disolves the clot.
Specific types of Magnetic Particles:
Bikram (US 2010/0003197) discloses a magnetic nanoparticle that includes an amine-functionalized metal-doped iron (III) oxide core, a lyer of gold seeding the amine-functionalized metal-doped iron oxide core, an outer gold-silver allow nanoshell and a targeting ligand attached to the nanoshell via a linker.
Magnetic microspheres (MMs):
Zhen (“A generic magnetic mirsophere platform with “clickable” ligands for purification and immobilizaiton of targeted proteins” (2015)) discloses functionalization of MMs with “clickable” ligands to capture corresponding tagged proteins.) Four widely used affinity ligands, including maltodextrin (MD) that binds to maltose binding protein, glutathione (GSH) that bins to gST tagged proteins, biotin that binds to streptavidin (SA) and O6–(4-aminomethyl-benzyl) guanine (BG) that binds to SNAP tagged prtoeins were used for immobilizaiotn of the corresponding proteins from cell lysates. The precursors of the four ligands present widely different reactive groups (-CHO, -SH, -COOH and -NH2) which can udnergo the alkynylation reaction and then “click” to teh surface of MMs. The MMs which can be funcitonalized to target a variety of different recombinant proteins may find applications in protein pruficaiton and screening processes.
–Immunomagnetic mirospheres:
Tang (US 17/628,754, published as US 20220395795) discloses a silver iron oxide (Ag-Fe3O4) immunomagnetic microsphere that includes poly-D-lysine modified on the surface and a S100B and/or MBP antibody linked to the poly-D-lysine by an amide bond.
Applications:
Metal nanoparticles possess interesting physical (structural, electronic, magnetic and optical) and chemical (catalytic) properties, thus they are used in many applications. Metal nanoparticles are usually deposited on carriers. Many supporting materials, icnluding siO2, TiO2, aluminum, active carbon, carbon nanotubes and graphene have been used for this purpose. Synthesis and applicaiton of functionalized magnetic composities have cause a great interst. Functionalized magentic composites are always synthesized based on a magnetic core and afterwards modifed with different compounds. These materials, due to their magentic properties, are easy to retrieve from the reaction system under a mangetic field. (Zhang, “Fabrication of magnetically recyclable Ag/CuFe3O4 nanoparticles with excellent catalytic activity for p-nitrophenol reduction” RSC Adv. 2014 4).
thermotherapy: can cause irreversible damage to disease cells (e.g., temperatures in a range from about 40-46C (hyperthermia) cause destruction of cancer cells, whereas healthy cells are capable of surviving up to about 46.5C). Lesniak (US 6,979,466) discloses using agents linked to nanoscale particles which are comprised of an iron oxide-containing core and at least two shells surrounding the core as well as at least one pharmacologically active species linked to the innermost shell. Such particles have applications in stroke and tumor therapy. With the use of a magnetic field, excitation of the iron oxide containing core occurs causing the generation of heat and thermoablation of the target region or causes heat induced lysis of clotted microcapillaries. Ivkov (US2005/0090732) discloses nanometer sized particles surrounded by polymer to form a bioprobe. When the particles are exposed to an externally applied alternative magnetic filed, the magnetic moments within each particle may respond by changing orientation which may result in the production of heat. The particles are attached to a target specific ligand such as an antibody.
Oscillation/vibration for therapy: Meretei (US 2006/0142632) discloses introducing ferrofluids locally which are then magnetically manipulated or moved throughout the blood vessels by an external magnetic field generator until the intended accumulated plaque is broken up and removed. Ueda (US 2011/0071335A1) also discloses that when magnetic nanoparticles are located in an affected area, such nanoparticles are oscillated by an alternating magentic field which causes the magnetic nanoparticles to break up. Schwartz (US 8,293,213) also discloses injecting magnetic particles into a bloodstream and moving a thrombus formed using a magnetic force to manipulate the magnetic particles. Chen (J. Drug Targeting, 2008, 16(4)) discloses T-PA loaded magnetic nano and microcarriers which are guided directly to the site of fascular occlusion by external magnetic fields.
Magnetic Resonance Imaging: The sensitivity of Magnetic resonance imaging (MRI) can be increased with contrast agents such as paramagnetic superparamagnetic iron oxide nanoparticles (SPIONs) and other magnetic nanoparticles. SPIONs are taken up by macrophages and are delivered by the reticulo endothelial system into healthy cells. Contrast for imaging results from the higher concentration of nanoparticles in healthy cells than in malignant cells. Leuschner (US2009/0169478) discloses magnetic nanoparticles either directly or through a spacer, bound to ligands with specificity for a target cell receptor. The specific accumulation in taregeted canacer cells enhances resolution for imaging.
Dectection of fibrosis and Thrombosis: ussat discloses fibrin binding peptides which can be conjugated to with a MRI detectable moiety such as for example a paramagnetic metal chelator or iron particles such as superparamagnetic FeO particles in order to form a contrast agent. The fibring binding peptides are used to detect and facilitate treatment of pathological conditions associated with the presence of fibrin such as thrombosis (US 2010/0158814).
Detection of inflammation: Negative enhancing agents such as desctran coated ultrasmall particles of iron oxide (USPIO, mean diameter 20-30 nm) can detect inflammation caused by cerebral ischemia, arthritis, nephrotoxic nephritis and renal transplant rejection in rates. The particles are internalized by cells, particularly monocytes and macrophages. Song-Kyung Jo (Kidney Interantional, 64 2003, 43-51 show that USPIO could enhance magnetic resonance imaging (MRP) and be used to detect inflammation in ishemic acute renal fialure (ARF) in rats. Hauger (Eur Radio 2007, 17(11) 2898-907, 2007 also showed that USPIO could be used to detect and characterize macrophage infiltration in native and transplanted kidneys.
Magnetic Resonance Propulsion: Untethered microdevices contain a ferromagnetic core and are propelled by mangetic forces indcued by the magnetic gradients generated with an MRI system (Magentic Resonance imaging). This method is ferred to as MRP (Magnetic Resonance Propulsion). In this context, an MRI system is not only used to image the region of interest, but also to propel a ferromagnetic microdevice and determine its location (Martel, US2010/0168553).