磁性水凝胶作为药物载体的应用研究进展

磁性水凝胶是一类同时具有磁性材料、高分子材料及水凝胶的性质特点的无机/有机复合材料。因具有优良的磁学性能及生物相容性,其作为新一代的药物载体可以实现磁响应、磁靶向及磁热疗等功能,在药物控制释放领域具有广阔的应用前景。对磁性水凝胶的制备方法及其在药物载体领域的研究情况进行了综述,详细介绍了磁性水凝胶作为药物载体的两种药物释放机理(ON/OFF模型及热敏释放原理),及其在磁靶向药物控释、磁热疗和磁共振成像方面的应用研究现状。     

Recent progress in Fe3O4 based magnetic nanoparticles: from synthesis to application

Fe₃O₄ based magnetic polymer nanoparticles (MPNPs) are densely studied for several decades. These Fe₃O₄ based MPNPs can be used in wastewater treatment and biological field such as magnetic resonance imaging contrast agents, hyperthermia therapy and protein separation. The Fe₃O₄ based MPNPs are attractive because they combine the advantages of magnetism and polymers together. In order to obtain the practical application in the above mentioned areas, the bare Fe₃O₄ needs to be functionalised with different kinds of molecules like organic small molecules and polymers and some inorganic molecules like silica, metals and carbon. In this review, the chemical preparation methods, different modification methods and various applications of the Fe₃O₄ based MPNPs are introduced.     

Giant Magnetic Heat Induction of Magnesium‐Doped γ‐Fe2O3 Superparamagnetic Nanoparticles for Completely Killing Tumors

Magnetic fluid hyperthermia has been recently considered as a Renaissance of cancer treatment modality due to its remarkably low side effects and high treatment efficacy compared to conventional chemotheraphy or radiotheraphy. However, insufficient AC induction heating power at a biological safe range of AC magnetic field (H_appl·f_appl < 3.0–5.0 × 10⁹ A m^?1 s^?1), and highly required biocompatibility of superparamagnetic nanoparticle (SPNP) hyperthermia agents are still remained as critical challenges for successful clinical hyperthermia applications. Here, newly developed highly biocompatible magnesium shallow doped γ‐Fe₂O₃ (Mg_0.13‐γFe₂O₃) SPNPs with exceptionally high intrinsic loss power (ILP) in a range of 14 nH m² kg^?1, which is an ≈100 times higher than that of commercial Fe₃O₄ (Feridex, ILP = 0.15 nH m² kg^?1) at H_appl·f_appl = 1.23 × 10⁹ A m^?1 s^?1 are reported. The significantly enhanced heat induction characteristics of Mg_0.13‐γFe₂O₃ are primarily due to the dramatically enhanced out‐of‐phase magnetic susceptibility and magnetically tailored AC/DC magnetic softness resulted from the systematically controlled Mg²⁺ cations distribution and concentrations in octahedral site Fe vacancies of γ‐Fe₂O₃ instead of well‐known Fe₃O₄ SPNPs. In vitro and in vivo magnetic hyperthermia studies using Mg_0.13‐γFe₂O₃ nanofluids are conducted to estimate bioavailability and biofeasibility. Mg_0.13‐γFe₂O₃ nanofluids show promising hyperthermia effects to completely kill the tumors.     

Preparation of magnetic mesoporous silica nanoparticles as a multifunctional platform for potential drug delivery and hyperthermia

We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with the potential multifunctionality of drug delivery and magnetic hyperthermia. Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat mesoporous silica shells for the formation of the core-shell structured MMS nanoparticles (MCN@C/mSiO₂), and the rattle-type structured MMS nanoparticles (MCN/mSiO₂) were obtained after the removal of the carbon layers from MCN@C/mSiO₂ nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles were investigated. The results revealed that the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had spherical morphology and average particle sizes of 390 and 320 nm, respectively. The MCN@C/mSiO₂ nanoparticles exhibited higher magnetic hyperthermia ability compared to the MCN/mSiO₂ nanoparticles, but the MCN/mSiO₂ nanoparticles had higher drug loading capacity. Both MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles had similar drug release behavior with pH-controlled release and temperature-accelerated release. Furthermore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles showed low cytotoxicity and could be internalized into HeLa cells. Therefore, the MCN@C/mSiO₂ and MCN/mSiO₂ nanoparticles would be promising for the combination of drug delivery and magnetic hyperthermia treatment in cancer therapy.     

Synthesis of Manganese Ferrite/Graphene Oxide Nanocomposites for Biomedical Applications

In this study, MnFe₂O₄ nanoparticle (MFNP)‐decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini‐emulsion and solvent evaporation process. It is demonstrated that the loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process. By fine‐tuning the sonication time, MGONCs as small as 56.8 ± 1.1 nm, 55.0 ± 0.6 nm and 56.2 ± 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are successfully fabricated. In order to improve the colloidal stability of MGONCs in physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs samples to an alternating magnetic field (AMF) show that the obtained nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1 mg Fe mL^?1 and under an 59.99 kA m^?1 field, the highest specific absorption rate (SAR) recorded is 1588.83 W g^?1 for MGONCs loaded with 14 nm MFNPs. It is also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI) T₂ contrast agents. A T₂ relaxivity value (r₂) as high as 256.2 (mM Fe)^?1 s^?1 could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity results show that PEGylated MGONCs exhibit an excellent biocompatibility that is suitable for biomedical applications.     

Magnetometry of Individual Polycrystalline Ferromagnetic Nanowires

Ferromagnetic nanowires are finding use as untethered sensors and actuators for probing micro‐ and nanoscale biophysical phenomena, such as for localized sensing and application of forces and torques on biological samples, for tissue heating through magnetic hyperthermia, and for microrheology. Quantifying the magnetic properties of individual isolated nanowires is crucial for such applications. Dynamic cantilever magnetometry is used to measure the magnetic properties of individual sub‐500 nm diameter polycrystalline nanowires of Ni and Ni₈₀Co₂₀ fabricated by template‐assisted electrochemical deposition. The values are compared with bulk, ensemble measurements when the nanowires are still embedded within their growth matrix. It is found that single‐particle and ensemble measurements of nanowires yield significantly different results that reflect inter‐nanowire interactions and chemical modifications of the sample during the release process from the growth matrix. The results highlight the importance of performing single‐particle characterization for objects that will be used as individual magnetic nanoactuators or nanosensors in biomedical applications.     

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.     

Magnetic nanoparticles coated with anacardic acid derived from cashew nut shell liquid

Magnetic nanoparticles functionalized with biomolecules have received special attention due to their various biomedical applications, such as drug delivery and magnetic hyperthermia treatment for cancer. In this study, we present the synthesis and characterization of new nanoparticles coated with anacardic acid derived from cashew nut shell liquid. The results showed that Fe₃O₄ nanoparticles coated with anacardic acid (AA-MAG) have superparamagnetic behavior and the magnetization is almost equal when compared with the pure Fe₃O₄. This coating provides stability by preventing the aggregation nanoparticles without losing its magnetization potential. The AA-MAG demonstrates excellent and fast magneto-temperature response which can be used as high-performance hyperthermia agents.     

Biocompatible nanoclusters of <Emphasis Type="Italic">O</Emphasis>-carboxymethyl chitosan-coated Fe<Subscript>3</Subscript>O<Subscript>4</Subscript> nanoparticles: synthesis,characterization and magnetic heating efficiency

In this work, we developed a polymer encapsulation of Fe₃O₄ nanoparticles as a core–shell nanocluster with different sizes to investigate the cluster structure effect on their magnetic properties and magnetic heating behavior. Well-dispersed nanoclusters of O-carboxymethyl chitosan-coated Fe₃O₄ nanoparticles were synthesized by microwave-assisted co-precipitation. The cluster sizes were tunable by varying the concentration of polymers used during synthesis. Nanoclusters present superparamagnetic behavior at room temperature with a reduction in saturation magnetization as a consequence of coating layer. The shift of blocking temperature to the higher value with increasing clusters size shows the stronger magnetic interaction in larger magnetic clusters. In a low alternating magnetic field with frequency of 178 Hz and amplitude of 103 Oe, nanoclusters offer a high heating efficiency. A maximum specific absorption rate of 204 W/g is observed in the sample with hydrodynamic size of 53 nm. In vitro cytotoxicity analysis performed on HeLa cells verified that nanoclusters show a good biocompatibility and can be an excellent candidate for applications in hyperthermia cancer treatment.     

Optimization of Pathogen Capture in Flowing Fluids with Magnetic Nanoparticles

Magnetic nanoparticles have been employed to capture pathogens for many biological applications; however, optimal particle sizes have been determined empirically in specific capturing protocols. Here, a theoretical model that simulates capture of bacteria is described and used to calculate bacterial collision frequencies and magnetophoretic properties for a range of particle sizes. The model predicts that particles with a diameter of 460 nm should produce optimal separation of bacteria in buffer flowing at 1 L h⁻¹. Validating the predictive power of the model, Staphylococcus aureus is separated from buffer and blood flowing through magnetic capture devices using six different sizes of magnetic particles. Experimental magnetic separation in buffer conditions confirms that particles with a diameter closest to the predicted optimal particle size provide the most effective capture. Modeling the capturing process in plasma and blood by introducing empirical constants (c_e), which integrate the interfering effects of biological components on the binding kinetics of magnetic beads to bacteria, smaller beads with 50 nm diameters are predicted that exhibit maximum magnetic separation of bacteria from blood and experimentally validated this trend. The predictive power of the model suggests its utility for the future design of magnetic separation for diagnostic and therapeutic applications.