Magnetofection: Magic magnetic nanoparticles for efficient gene delivery

Magnetic nanoparticles (MNPs) have become a research hotspot and widely used in the biomedical field in recent decades due to their unique magnetic properties. This minireview summarizes the specific gene transfection of magnetic particles (magnetofection) during eversy dynamic process of gene delivery (gene binding, cellular uptake, endosomal escape, intracellular trafficking and in vivo targeting). Meanwhile, the synergistic biomedical application of magnetofection and the effects of MNPs have also been discussed, including magnetic resonance imaging (MRI), magnetic mediated hyperthermia (MMH), Fenton reaction and autophagy. Finally, the clinical prospect of magnetofection was briefly expected.     

Synthesis,functionalization, and nanomedical applications of functional magnetic nanoparticles

This review summarizes the current synthesis of magnetic nanoparticles (MNPs) preparation, functionalization and stabilization methods. And furthermore it highlights some actual case analyses of these MNPs for disease therapy, drug delivery, hyperthermia, bioseparation and bioimaging applications.     

Colloidal micelles of block copolymers as nanoreactors,templates for gold nanoparticles,and vehicles for biomedical applications

Target drug delivery methodology is becoming increasingly important to overcome the shortcomings of conventional drug delivery absorption method. It improves the action time with uniform distribution and poses minimum side effects, but is usually difficult to design to achieve the desire results. Economically favorable, environment friendly, multifunctional, and easy to design, hybrid nanomaterials have demonstrated their enormous potential as target drug delivery vehicles. A combination of both micelles and nanoparticles makes them fine target delivery vehicles in a variety of biological applications where precision is primarily required to achieve the desired results as in the case of cytotoxicity of cancer cells, chemotherapy, and computed tomography guided radiation therapy.     

Immobilized manganese porphyrin on functionalized magnetic nanoparticles via axial ligation: efficient and recyclable nanocatalyst for oxidation reactions

Magnetic nanoparticles (MNPs), Fe₃O₄@SiO₂, have been prepared and functionalized by 3-(chloropropyl)trimethoxysilane and then by imidazole to synthesize Fe₃O₄@SiO₂-Im. The functionalized Fe₃O₄ nanoparticles were used as a support to anchor manganese porphyrin via axial ligation. The prepared catalyst was characterized by elemental analysis, FT-IR spectroscopy, X-ray powder diffraction, UV–vis spectroscopy, and scanning electron microscopy. Application of immobilized manganese porphyrin as a heterogeneous catalyst in oxidation of alkenes and sulfides was explored. To find suitable reaction conditions, effect of different parameters such as solvent and temperature on immobilization process and also various reaction parameters (oxidant, solvent, and time) on oxidation reactions has been investigated. The results showed that the immobilized Mn-porphyrin on functionalized MNPs is an efficient and reusable catalyst for oxidation of substrates.     

PEO coated magnetic nanoparticles for biomedical application

This paper reports on the preparation, characterization and stealthiness of superparamagnetic nanoparticles (magnetite Fe₃O₄) with a 5 nm diameter and stabilized in water (pH ? 6.5) by a shell of water-soluble poly(ethylene oxide) (PEO) chains. Two types of diblock copolymers, i.e., poly(acrylic acid)-b-poly(ethylene oxide), PAA-PEO, and poly(acrylic acid)-b-poly(acrylate methoxy poly(ethyleneoxide)), PAA-PAMPEO, were prepared as stabilizers with different compositions and molecular weights. At pH ? 6.5, the negatively ionized PAA block interacts strongly with the positively-charged nanoparticles, thus playing the role of an anchoring block. Aggregates of coated nanoparticles were actually observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter was in the 50-100 nm range and the aggregation number (number of nanoparticles per aggregate) was lying between several tens and hundred. Moreover, the stealthiness of these aggregates was assessed “in vitro” by the hemolytic CH50 test. No response of the complement system was observed, such that biomedical applications can be envisioned for these magnetic nanoparticles. Preliminary experiments of magnetic heating (10 kA/m; 108 kHz) were performed and specific absorption rate varied from 2 to 13 W/g_(Fe).     

A reactive oxygen species-responsive dendrimer with low cytotoxicity for efficient and targeted gene delivery

Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene ca rriers with high delivery efficiency and low cytotoxicity has long been a key project.Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics.However,when they are used as gene carrier,the gene transfection efficiency is not satisfactory.Herein,a novel thioketal-core polyamidoamine dendrimer(i.e.,ROS...     

Inorganic hybrid nanoparticles in cancer theranostics: understanding their combinations for better clinical translation

Drug resistance, tumor heterogeneity, and poor selectivity make cancer treatment with current modalities a challenging and complicated task. Careful planning of diagnosis and therapy is required to build new strategies for treatment and management of cancer. The amalgamation of therapeutics and diagnostics in a single nano agent, known as theranostics is now possible due to the emergence of nanotechnology. Theranostics offers opportunities for personalized medicine by real-time monitoring of drug accumulation and dynamic modification of treatment depending on individual patient needs. Thus potential to reform disease management is held by theranostic nanoparticles. Amongst other nanosystems, inorganic nanoparticles have been widely used for developing theranostic drug delivery systems due to their favorable intrinsic properties. The last decade has seen a surge in development of such theranostic nanoparticles in which various inorganic materials in different combinations have been engineered to maximize the output with respect to specific applications. For example, Fe₃O₄@Au nanoparticles were developed for MRI, hyperthermia and magnetically controlled drug delivery. Several such combinations leading to innovative theranostic applications and their underlying mechanisms have been highlighted in this review. A review of patents and clinical trials of inorganic theranostic nanoparticles is also presented through which we understood that clinical translation still remains in the nascent stage. Thus, it is necessary to find and understand reasons for lack of clinical translations. Therefore, we have discussed the challenges associated with bench-to-bed translation of such inorganic nanoparticles which show immense potential in vitro but fail to deliver in long run.     

Folate-decorated succinylchitosan nanoparticles conjugated with doxorubicin for targeted drug delivery

Amphiphilic biodegradable succinylchitosan nanoparticles modified with folic acid are described that act as an emulsifier to form nanoparticles. Their molecular structures and physicochemical as well as self‐assembly properties are characterized by means of FT‐IR, ¹H NMR, FESEM, DLS, and TEM. The nanoparticles are 60–80 nm in size and are not toxic in vitro. They are immobilized with the cytostatic drug doxorubicin. Specific transport of doxorubicin by the nanoparticles into the folate‐receptor‐overexpressing cancer cells and its biological activity as well as in vitro release are demonstrated. It is shown that under acidic condition more drug is released. The nanoparticles can thus not only specifically deliver doxorubicin to its target, but also release the drug depending on the pH.

     

Biocompatible core-shell nanoparticle-based surface-enhanced Raman scattering probes for detection of DNA related to HIV gene using silica-coated magnetic nanoparticles as separation tools

A novel, highly selective DNA hybridization assay has been developed based on surface-enhanced Raman scattering (SERS) for DNA sequences related to HIV. This strategy employs the Ag/SiO₂ core-shell nanoparticle-based Raman tags and the amino group modified silica-coated magnetic nanoparticles as immobilization matrix and separation tool. The hybridization reaction was performed between Raman tags functionalized with 3′-amino-labeled oligonucleotides as detection probes and the amino group modified silica-coated magnetic nanoparticles functionalized with 5′-amino-labeled oligonucleotides as capture probes. The Raman spectra of Raman tags can be used to monitor the presence of target oligonucleotides. The utilization of silica-coated magnetic nanoparticles not only avoided time-consuming washing, but also amplified the signal of hybridization assay. Additionally, the results of control experiments show that no or very low signal would be obtained if the hybridization assay is conducted in the presence of DNA sequences other than complementary oligonucleotides related to HIV gene such as non-complementary oligonucleotides, four bases mismatch oligonucleotides, two bases mismatch oligonucleotides and even single base mismatch oligonucleotides. It was demonstrated that the method developed in this work has high selectivity and sensitivity for DNA detection related to HIV gene.     

Magnetic hydroxyapatite nanoparticles: An efficient adsorbent for the separation and removal of nitrate and nitrite ions from environmental samples

A novel type of magnetic nanosorbent, hydroxyapatite‐coated Fe₂O₃ nanoparticles was synthesized and used for the adsorption and removal of nitrite and nitrate ions from environmental samples. The properties of synthesized magnetic nanoparticles were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and X‐ray powder diffraction. After the adsorption process, the separation of γ‐Fe₂O₃@hydroxyapatite nanoparticles from the aqueous solution was simply achieved by applying an external magnetic field. The effects of different variables on the adsorption efficiency were studied simultaneously using an experimental design. The variables of interest were amount of magnetic hydroxyapatite nanoparticles, sample volume, pH, stirring rate, adsorption time, and temperature. The experimental parameters were optimized using a Box–Behnken design and response surface methodology after a Plackett–Burman screening design. Under the optimum conditions, the adsorption efficiencies of magnetic hydroxyapatite nanoparticles adsorbents toward NO₃^? and NO₂^? ions (100 mg/L) were in the range of 93–101%. The results revealed that the magnetic hydroxyapatite nanoparticles adsorbent could be used as a simple, efficient, and cost‐effective material for the removal of nitrate and nitrite ions from environmental water and soil samples.     

Synthesis and surface engineering of magnetic nanoparticles for environmental cleanup and pesticide residue analysis: A review

In recent years, water pollution and pesticide accumulation in the food chain have become a serious environmental and health hazard problem. Direct determination of these contaminants is a difficult task due to their low concentration level and the matrix interferences. Therefore, an efficient separation and preconcentration procedure is often required prior to the analysis. With the advancement in nanotechnology, various types of magnetic core–shell nanoparticles have successfully been synthesized and received considerable attention as sorbents for decontamination of diverse matrices. Magnetic core–shell nanoparticles with surface modifications have the advantages of large surface‐area‐to‐volume ratio, high number of surface active sites, no secondary pollutant, and high magnetic properties. Due to their physicochemical properties, surface‐modified magnetic core–shell nanoparticles exhibit high adsorption efficiency, high rate of removal of contaminants, and easy as well as rapid separation of adsorbent from solution via external magnetic field. Such facile separation is essential to improve the operation efficiency. In addition, reuse of nanoparticles would substantially reduce the treatment cost. In this review article, we have attempted to summarize recent studies that address the preconcentration methods of pesticide residue analysis and removal of toxic contaminants from aquatic systems using magnetic core–shell nanoparticles as adsorbents.     

Self-assembly strategy for the preparation of polymer-based nanoparticles for drug and gene delivery

Nanoparticulate drug-delivery systems have attained much importance because of their injectable property, the possibility to achieve passive targeting and active targeting, and unique advantages to realize stimuli tailored delivery. Molecular self-assembly is a powerful method for fabricating polymer-based nanoparticles, which involves various driving forces, such as hydrophobic interactions, electrostatic interactions, stereocomplexation, host/guest interactions and hydrogen bonding. By fine tuning one or many types of these interactions, self-assemblies with a wide range of structures and functions could be fabricated. In this article, recent developments in different self-assembly strategies for the preparation of polymer-based nanoparticulate delivery systems are discussed.     

Functional polymer/inorganic hybrid nanoparticles for macrophage targeting delivery of oligodeoxynucleotides in cancer immunotherapy

To efficiently deliver CpG oligodeoxynucleotides (ODN) in cancer immunotherapy, a multifunctional macrophage targeting delivery system was designed and prepared. Mannosylated carboxymethyl chitosan/protamine sulfate/CaCO₃/ODN (MCMC/PS/CaCO₃/ODN) nanoparticles were prepared using a facile self-assembly method. The functional components, including MCMC to endow the nanoparticles with macrophage targeting ability, PS to improve the ODN loading capacity and enhance the cell uptake, and CaCO₃ to encapsulate ODN and induce the favorable pH sensitivity, were introduced to the delivery systems by self-assembly. Due to the mannose mediated endocytosis and the favorable effects of PS in overcoming delivery barriers, MCMC/PS/CaCO₃/ODN nanoparticles exhibit a much higher ODN delivery efficiency and a significantly enhanced immune stimulation capacity as compared with Lipofectamine 2000/ODN complexes. The regulation of NF-κB activity by our ODN delivery system results in dramatically increased production of proinflammatory cytokines including IL-12, IL-6, and TNF-α in RAW264.7 cells. The significantly increased CD80 expression after stimulation by the ODN delivery systems indicates the successful modulation of the macrophage polarity to the anti-tumor M1 phenotype. The multifunctional macrophage targeting delivery system developed has promising applications in delivery of CpG ODN in cancer immunotherapy.     

Fabrication of tunable microreactor with enzyme modified magnetic nanoparticles for microfluidic electrochemical detection of glucose

A microfluidic device was designed for amperometric determination of glucose by packing enzyme modified magnetic nanoparticles (MNPs) in its microchannel as an enzyme microreactor. Glucose oxidase was covalently attached to the surface of MNPs and localized in the microchannel by the help of an external magnetic field, leading to a tunable packing length. By changing the length of microreactor from 3 to 10 mm, the performance for glucose detection was optimized. The optimal linear range to glucose was from 25 μM to 15 mM with a detection limit of 11 μM at a length of 6 mm. The inter- and intra-day precisions for determination of 1.0 mM glucose were 0.8% and 1.7%, respectively, and the device-to-device reproducibility was 95.6%. The enzyme reactor remained its 81% activity after three-week storage. Due to the advantages of the device and fracture sampling technique, serum samples could be directly sampled through the fracture to achieve baseline separation from ascorbic acid, and proteins in the samples did not interfere with the detection. This work provided a promising way for pretreatment-free determination of glucose with low cost and excellent performance.     

On-chip fabrication of mutifunctional envelope-type nanodevices for gene delivery

Microfluidic devices may be highly beneficial to the rapid fabrication of small quantities of various nonviral vectors with different functionalities, which is indispensable for effective order-made gene therapy. We adapted a microfluidic chip-based approach for fabricating small quantities of nonviral vectors in a short time in preparation for order-made gene therapy applications. This approach permitted us to fabricate multifunctional envelope-type nanodevices (MENDs), composed of a compacted (or condensed) DNA core and a lipid bilayer membrane shell, which are considered as promising nonviral vectors for gene therapy applications. The on-chip fabrication of the MEND was very simple, rapid, convenient, and cost-effective compared with conventional methods. The size of the MEND showed strong dependence on the concentration and flow rate of the reaction precursors and could be controlled to be much smaller than that achievable by conventional methods. This, together with abovementioned merits, makes our microfluidic chip-based approach very attractive for the fabrication of MENDs for effective application to order-made gene therapy.     

Ni ion-containing immobilized ionic liquid on magnetic Fe3O4 nanoparticles: An effective catalyst for the Heck reaction

In this work, we synthesized Ni²⁺-containing 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium chloride ionic liquid on magnetic Fe₃O₄ nanoparticles. The catalytic activity of these novel nanocomposites was finally evaluated for the Heck reaction at 100 °C, and can be reused after washing without loss in activity. The immobilized ionic liquid catalysts proved to be effective and easily separated from the reaction media by applying an external magnetic field. This procedure has many obvious advantages compared to those reported in the previous literature, including avoidance of the use of the expensive Pd catalysts, mild reaction conditions, high yields, and simplicity of the methodology.     

Using baicalin-functionalized magnetic nanoparticles for selectively extracting flavonoids from Rosa chinensis

An extraction agent featuring a natural product, baicalin, anchored on the surface of nanomagnetic particles (BMNPs) is herein reported. A facile solid-phase extraction (SPE) procedure with high selectivity toward flavonoids using BMNPs has been established. BMNPs were proven very effective for enriching flavonoids from extracts of medicinal plants such as Rosa chinensis. The SPE protocol involving a convenient solid-liquid separation by using an external magnet field was easy to carry out. Further, the SPE sorbent (BMNPs) could be reused for many times reducing the operation cost. Importantly, flavonoids retained on the BMNPs were effectively recovered by eluting with methanol. Coupling the proposed SPE with ESI-MS/MS allowed a quick quantification of flavonoids in herbal extracts. Simultaneous determination of eight flavonoids extracted from R. chinensis was demonstrated in this work.     

The effect of magnetic nanoparticles upon the smectic-A to smectic-C* phase transition

We report on wide-angle X-ray scattering measurements along the smectic-A to chiral ferroelectric smectic-C* phase transition of the liquid crystal SCE9 and its mixture with maghemite magnetic nanoparticles of typical dimension 20 nm. The temperature profiles of the tilt angle are fitted by an extended mean-field model. Neither pre-transitional order effects nor variations in the SmA layer thickness are observed, indicating a rather negligible influence of these nanoparticles upon the molecular orientation at the smectic-A to smectic-C* phase transition of SCE9. These results are very different from what was observed for smaller CdSe nanoparticles (3.5 nm) where both a dilation of the smectic layers in the SmA phase and a crossover behaviour for the smectic-A to smectic-C* transition away from tricriticality have been observed for analogous concentrations.