Magnetic Nanoparticles in Human Health and Medicine. Группа авторов

NPs in vivo enable strong image contrast of targeted anatomical sites, also sense the local molecular environments to catalyze contrast switching. In ex vivo diagnostics, magnetic nanomaterials are seamlessly incorporated into reduced biosensing platforms, thereby enabling the detection of rare and diverse molecular targets without requiring for extensive sample preparation. From these synergistic developments, it is likely that magnetic detection will have broad applications in biomedical research as well as clinical transformation. Nowadays, tumor morbidity is increasing, and early tumor diagnosis is of vital importance. MRI is one of the common methods for tumor diagnosis (Shokrollahi et al. 2014).

Figure 1.21 Different applications of magnetic NPs.

      Anbarasu et al. (2015) labeled the PEG‐coated Fe₃O₄ NPs with a monoclonal antibody and then implanted it into the colon cancer mouse model. They successfully conducted targeted localization by MRI. Stem cell has attracted widespread attention in research on biomedicine owing to its excellent proliferative capacity and differentiation potential. Presently, there are two methods to label stem cells using superparamagnetic NPs. Additionally, cells injected into the tumor tissue were recognized histologically to be the superparamagnetic NP‐labeled stem cells. The function and activity of these cells are not affected, suggesting that superparamagnetic NPs can be used for labeling stem cells (Kim et al. 2016; Guo et al. 2018). Magnetic nanoparticles based on a novel nano biosensor have been developed by Grimm et al. (2004) for rapid screening of telomerase activity in biological samples (Kaittanis et al. 2009). Hassen et al. (2008) defined a method based on DNA hybridization to detect the hepatitis B virus using the nonfaradic electrochemical impedance spectroscopy method. They modified DNA probes with biotin on streptavidin‐based magnetic nanoparticles and then immobilized nanoparticles onto the bare gold electrode using a magnet. Sayhi et al. (2018) developed a technique with the aim of isolation and detection of influenza A virus H9N2 subtype. They first attached an anti‐matrix protein 2 antibody to iron magnetic nanoparticles (Saylan et al. 2019).

Superparamagnetic nanoparticles are beneficial for cell‐tracking and for calcium sensing. Ferrofluids consist of a magnetic core surrounded by a polymeric layer coated with antibodies for capturing cells (Atanasijevic et al. 2006). Superparamagnetic nanoparticles with 2–3 nm sizes have been used in conjunction with MRI to reveal small and otherwise undetectable lymph‐node metastases. A dextran‐coated iron oxide nanoparticle increases MRI visualization of intracranial tumors for more than 24 hours (Gao et al. 2014). Ma et al. (2011) presented a novel method of cocaine detection. They used a fluorescence biosensor based on aptamer and rolling circle amplification of short DNA strand separated by magnetic beads. The cocaine aptamers were immobilized onto gold nanoparticles functionalized magnetic beads hybridized with short DNA strand. The rolling circle magnification and the separation by magnetic beads decrease the background signal. Furthermore, compared with other reported cocaine sensors, their method exhibited excellent sensitivity. In addition, new strategy may provide a platform for the detection of numerous proteins and low molecular weight analytes.

      1.2.2 Magnetic NPs as a Smart Drug Delivery System

      Magnetic NPs play a vital role in targeted drug delivery of molecules which improve the drug specificity and reduce the side effect (Enpuku et al. 2001). This approach has also recently been used for magnetic targeting of magnetoliposomes within solid tumors (Fortin‐Ripoche et al. 2006). The liposome filled with magnetic nanoparticles (magnetoliposomes) is highly potential drug carrier and has the advantage to allow at the same time magnetic resonance imaging detection (Martina et al. 2005), making possible noninvasive validation of magnetic targeting (Riviere et al. 2006). In cancer chemotherapeutic treatment, therapeutic compounds with high cytotoxic activities need to be delivered into individual tumor cells to damage or kill them. In the conventional methods, the accumulation of these drugs in the tumor and healthy tissue is equivalent due to the nonspecific nature of drugs injected into the blood systems (Bao et al. 2013). This occurrence gives rise to the side effects such as normal healthy cells are attacked in the procedure of treatment.

      Magnetic NPs mediated and targeted drug delivery of molecules can improve the drug specificity and reduce this side effect (Jain 2001). Therapeutic agent attached or encapsulated within magnetic NPs lead to formation of MNPs/therapeutic agent co‐complex. These magnetic carriers are injected into the bloodstream and directed to focus on the tumor location through external applied inhomogeneous magnetic fields (McBain et al. 2008). Magnetic NPs functionalized with the drug in targeted drug delivery can increase the biodistribution and protect the drugs from the microenvironment, exhibiting higher internalization by cancer cells than healthy cells and permitting the usage of the therapeutic agents at low enough doses to decrease the toxicity of chemotherapy (Pankhurst et al. 2003).

A number of studies have confirmed the number of advantages of magnetic NPs for drug delivery. Pankhurst et al. (2003) proved that the targeted delivery technique using magnetic nanoparticles was a major breakthrough to the treatment of many diseases in the clinical practice in current years. Therapeutic compounds are attached to biocompatible magnetic nanoparticles, and the applied magnetic fields are focused on specific targets in vivo. The fields capture the particle complex and result in improved delivery to the target site (Xu and Sun 2012). Magnetic NPs are as carriers for drugs and genes targeted drug delivery and has been one of the most desirable applications of MNPs for chemotherapy (Pankhurst et al. 2003). The application of MNPs for regenerative medicine is based on the noninvasive nature of MRI for transplanted stem cells. MRI provides excellent soft‐tissue contrast with high resolution and can be used for visualization of single cells against a homogeneous background. Usually, iron oxide NPs were loaded into stem cells by passive internalization. The introduction of surface coatings or target ligands may further increase the uptake by cells. There is plenty of research on stem cell tracking by MNP‐aided MRI methodology (Bulte et al. 2002; Bulte and Kraitchman 2004). The use of therapeutic cells, proteins, and nucleic acids in the treatment of various conditions is a highly active area of research (Mok and Zhang 2013); their innate specificity makes such biotherapeutics attractive potential treatments. The ineffective delivery systems frequently hamper the application of biotherapeutics. To overcome this, novel magnetically driven delivery systems have been developed to facilitate the fast, efficient, and site‐specific delivery of biotherapeutic interferences (Chomoucka et al. 2010).

      1.2.3 Magnetic NPs in Therapeutic Applications

      Magnetic NPs established various biomedical and therapeutic applications. Magnetic NPs coated with natural polymers (such as carbohydrates and proteins) are common. Moreover, many natural polymers are biocompatible and are therefore suitable for coating NPs for biomedical applications such as cancer treatment (White et al. 2006; Arruebo et al. 2007). The important reason is the low payload capacity of existing MNPs because payload (i.e. drugs) can only be attached on the surface or encapsulated in the double‐layer coating around MNPs. An innovative platform of engineered Fe₃O₄ porous hollow NPs (HMNPs) was strategic for the controlled release of cisplatin. Cisplatin was embedded in the interior cavities and the targeting agent. Herceptin was attached to the surface of magnetic NPs. These NPs could then well target and deliver cisplatin to ErbB2‐/Neu‐positive breast cancer cells (SK‐BR‐3). Several times the therapeutic agents are packed in the magnetic NP that are then released to destroy the tumor cell effectively (Niemirowicz et al. 2012).

      In genetic disease diagnosis, the identification of mutated forms of genes becomes important as a prognostic marker for other pathologies, especially cancer. Jangpatarapongsa et al. (2011) revealed a novel tool for the detection of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). It was a magneto‐polymerase chain reaction (PCR)‐enzyme linked gene technique. The amine‐functionalized primers were covalently attached to the surface of carboxyl‐functionalized magnetic nanoparticles. This modification allowed a convenient separation of PCR products with high sensitivity (0.5 pg ml⁻¹) and high specificity using material obtained