Surface Of Superparamagnetic Iron Oxide Nanoparticles Research Articles

Influence of SPION Surface Coating on Magnetic Properties and Theranostic Profile.

This study aimed to develop multifunctional nanoplatforms for both cancer imaging and therapy using superparamagnetic iron oxide nanoparticles (SPIONs). Two distinct synthetic methods, reduction-precipitation (MR/P) and co-precipitation at controlled pH (MpH), were explored, including the assessment of the coating's influence, namely dextran and gold, on their magnetic properties. These SPIONs were further functionalized with gadolinium to act as dual T1/T2 contrast agents for magnetic resonance imaging (MRI). Parameters such as size, stability, morphology, and magnetic behavior were evaluated by a detailed characterization analysis. To assess their efficacy in imaging and therapy, relaxivity and hyperthermia experiments were performed, respectively. The results revealed that both synthetic methods lead to SPIONs with similar average size, 9 nm. Mössbauer spectroscopy indicated that samples obtained from MR/P consist of approximately 11-13% of Fe present in magnetite, while samples obtained from MpH have higher contents of 33-45%. Despite coating and functionalization, all samples exhibited superparamagnetic behavior at room temperature. Hyperthermia experiments showed increased SAR values with higher magnetic field intensity and frequency. Moreover, the relaxivity studies suggested potential dual T1/T2 contrast agent capabilities for the coated SPpH-Dx-Au-Gd sample, thus demonstrating its potential in cancer diagnosis.

Surface Modifications of Superparamagnetic Iron Oxide Nanoparticles with Polyvinyl Alcohol, Chitosan, and Graphene Oxide as Methylene Blue Adsorbents

Synthetic dye contamination of wastewater has long been a social issue, with adsorption being the most focused upon research technique among wastewater treatment. Using the co-precipitation method, superparamagnetic iron oxide nanoparticles (SPIONs) with the size of 13.6 ± 1.9 nm were synthesized. By adsorbing methylene blue (MB) on the modified surface of SPIONs using polyvinyl alcohol, chitosan, and graphene oxide, the entrapment efficiency at pH 7 can be up to 87.00 ± 0.16% after 13 days, and the highest MB loading capacity was 3.638 ± 0.009%, while the highest loading amount achieved was 36.385 ± 0.095 mg/g. The cumulative desorption capacity of the adsorbent at pH 3.8 was at its maximum at 8.94 ± 0.66% after 30 days. The results of the experiments indicated that the compound has a favorable impact on the adsorption of synthetic dyes; nevertheless, more research is needed to determine the ideal ratio, temperature, and pH levels for this chemical.

Magnetic in situ determination of surface coordination motifs by utilizing the degree of particle agglomeration

Most analytical techniques used to study the surface chemical properties of superparamagnetic iron oxide nanoparticles (SPIONs) are barely suitable for in situ investigations in liquids, where SPIONs are mostly applied for hyperthermia therapy, diagnostic biosensing, magnetic particle imaging or water purification. Magnetic particle spectroscopy (MPS) can resolve changes in magnetic interactions of SPIONs within seconds at ambient conditions. Herein, we show that by adding mono- and divalent cations to citric acid capped SPIONs, the degree of agglomeration can be utilized to study the selectivity of cations towards surface coordination motifs via MPS. A favored chelate agent, like ethylenediaminetetraacetic acid (EDTA) for divalent cations, removes cations from coordination sites on the SPION surface and causes redispersion of agglomerates. The magnetic determination thereof represents what we call a “magnetically indicated complexometric titration”. The relevance of agglomerate sizes for the MPS signal response is studied on a model system of SPIONs and the surfactant cetrimonium bromide (CTAB). Analytical ultracentrifugation (AUC) and cryogenic transmission electron microscopy (cryo-TEM) reveal that large micron-sized agglomerates are required to significantly change the MPS signal response. With this work, a fast and easy-to-use characterization method to determine surface coordination motifs of magnetic nanoparticles in optically dense media is demonstrated.

Plasmid-DNA Delivery by Covalently Functionalized PEI-SPIONs as a Potential 'Magnetofection' Agent.

Nanoformulations for delivering nucleotides into cells as vaccinations as well as treatment of various diseases have recently gained great attention. Applying such formulations for a local treatment strategy, e.g., for cancer therapy, is still a challenge, for which improved delivery concepts are needed. Hence, this work focuses on the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) for a prospective "magnetofection" application. By functionalizing SPIONs with an active catechol ester (CafPFP), polyethyleneimine (PEI) was covalently bound to their surface while preserving the desired nanosized particle properties with a hydrodynamic size of 86 nm. When complexed with plasmid-DNA (pDNA) up to a weight ratio of 2.5% pDNA/Fe, no significant changes in particle properties were observed, while 95% of the added pDNA was strongly bound to the SPION surface. The transfection in A375-M cells for 48 h with low amounts (10 ng) of pDNA, which carried a green fluorescent protein (GFP) sequence, resulted in a transfection efficiency of 3.5%. This value was found to be almost 3× higher compared to Lipofectamine (1.2%) for such low pDNA amounts. The pDNA-SPION system did not show cytotoxic effects on cells for the tested particle concentrations and incubation times. Through the possibility of additional covalent functionalization of the SPION surface as well as the PEI layer, Caf-PEI-SPIONs might be a promising candidate as a magnetofection agent in future.

Interaction of doxorubicin delivered by superparamagnetic iron oxide nanoparticles with DNA

We studied the interaction of superparamagnetic iron oxide nanoparticles (SPIONs), covered by trisodium citrate, with doxorubicin (DOX) and DNA using the spectrophotometric method. We calculated the binding parameters in the binary (DOX-SPION and SPION-DNA) and the ternary (DOX-SPION-DNA) systems. Our studies showed that the nanoparticles do not interact with DNA. We also observed that one nanoparticle loads rather a large number of DOX molecules with a quite high binding constant value (kDOX-SPION = 1.2 × 104 M−1). The DNA addition to the DOX-SPION system induces DOX release from the SPION surface and the formation of DOX-DNA complexes. The presence of nanoparticles has almost no effect on the constant of doxorubicin binding to DNA (kDOX-DNA ≈ 3 × 104 M−1). At high DNA concentrations, almost all DOX molecules bind to DNA. Accordingly, the use of SPIONs as DOX carriers does not require an increased drug dose to achieve a therapeutic effect. Thus, SPIONs are perspective nanocarriers for DOX delivery.

Synthesis of Candida Antarctica Lipase B (CALB) enzyme-powered magnetite nanomotor based on PCL/Chitosan Janus nanostructure

In this work, we report the design and synthesis of internal energy-driven Janus nanomotors (JNMs), which are composed of certain reactive materials that are capable of converting chemical energy in the backbone of nanomotors into kinetic energy. For this purpose, superparamagnetic iron oxide nanoparticles (SPIONs) with the anisotropic surface were obtained via a Pickering emulsion. Modified chitosan (as hydrophilic polymer) and functionalized polycaprolactone (as hydrophobic domain) were covalently linked to the surface of bi-functional SPIONs to produce Janus nanoparticles (JNPs). Then, the CALB enzyme was loaded in the PCL hemisphere of JNPs to form the Janus nanomotor. When nanomotors are placed in the phosphate-buffered saline solution, the driving force for motion is provided by the decomposition of polyester into monomers and oligomers on one side of the JNMs. The trajectories of the nanomotors were recorded under different circumstances by a video microscope and analyzed by the mean squared displacement. The results show that the velocity of JNMs increases with an increasing percentage of the loaded enzyme. In addition, the diffusion coefficient enhances up to 87.67% in compared with nanoparticles without enzyme. Controlling the motion direction of JNMs by an external magnetic field is also possible, due to the presence of SPIONs.

Development of novel poly-l-lysine-modified sericin-coated superparamagnetic iron oxide nanoparticles as siRNA carrier

Small interfering RNA (siRNA) is a promising therapeutic modality, however, its successful clinical application is still challenging due to the lack of safe and efficient carrier systems. Superparamagnetic iron oxide nanoparticles (SPIONs)-based drug or gene carrier systems have displayed tremendous promise in nanomedicine. They possess intrinsic unique superparamagnetism that provides them to be concentrated in the targeted therapeutic site of action where an external magnetic field is applied. SPIONs can be also designed as theranostic agents to achieve simultaneous therapeutic and diagnostic purposes. Despite these favorable features, SPIONs are colloidally unstable and can be easily eliminated in the circulation. More importantly, the toxicological concerns associated with SPIONs, which often lead to the generation of reactive oxygen species (ROS), need to be thoroughly considered. Various types of polymers have been proposed so far to cover the surface of SPION to overcome these disadvantages. Silk protein, sericin can be ideal as a coating material due to its high biocompatibility, good biodegradability, and in vivo stability. In terms of the development of SPIONs as siRNA carriers, to the best of our knowledge, no protein was used as the coating material, and SPIONs coated with sericin have not been reported in the literature as a drug or gene carrier system. The present study aimed to design and develop a novel siRNA carrier system based on SPIONs. We prepared and characterized a nanomaterial comprised of SPIONs covalently coated with a biocompatible protein, sericin (Ser), and modified with a cationic polymer, poly- l -lysine (PLL) to incorporate the negatively charged siRNA. Transmission electron microscopy (TEM) images revealed that obtained nanoparticles had narrow size distribution with spherical shape and coated nanoparticles presented black spheres in the SPION core surrounded with a gray layer, which indicated sericin coating. Adding PLL to Ser-SPIONs did not cause any dramatic change in nanoparticle size whereas it provided a net positive charge to the particles. Additionally, electron spin resonance (ESR) analysis showed that sericin coating and PLL modification did not efface the superparamagnetic properties of the particles. We successfully attached the control-siRNAs to the surface of PLL/Ser-SPIONs, forming siRNA-PLL/Ser-SPION nanoplatforms and achieving high siRNA binding efficiencies ranged between 81.90% and 93.50%. The ability of SPIONs-based nanocarriers to fulfill their promises in clinical use depends on keeping their nanotoxicity properties to a minimum. All the nanoparticle formulations tested herein were found to be biocompatible against non-cancerous and cancer cells by cytotoxicity assays. We also investigated the effect of resulting bare particles, PLL/Ser-SPIONs, on the clonogenicity of cancer cells. According to the results, the cells exhibited colony formation ability depending on the concentration of the nanoparticles and PLL/Ser-SPIONs did not block clonogenicity, except at very high doses. Taken together, our findings imply that these new PLL/Ser-SPIONs can be considered as a safe and promising carrier candidate to be used and developed for further siRNA-based applications. • A new siRNA nanocarrier system composed of SPIONs coated with sericin, and modified with PLL was successfully synthesized.. • High siRNA binding efficiency was achieved by incorporating the siRNA with the PLL/Ser-SPIONs. • siRNA loaded PLL/Ser-SPIONs exhibited sustained in vitro siRNA release kinetics. • Cytotoxicity and colony formation assays revealed that PLL/Ser-SPIONs were biocompatible and safe materials. • Our work suggests that PLL/Ser-SPIONs can be a promising siRNA carrier candidate for gene silencing therapies.

Anisotropic modification of SPIONs surface with thiol and alkyne groups for fabrication of poly (2-hydroxyethyl methacrylate)/polydopamine amphiphilic Janus nanoparticles via double-click reaction

The Janus nanoparticles (JNPs) have been considered as dual-functionalized devices. One of the materials which can be used in the hybrid Janus nanoparticles is superparamagnetic iron oxide nanoparticles (SPIONs). In this work, a novel procedure based on anisotropic surface modification of SPIONs through Pickering Emulsion was utilized to obtain bi-functional SPIONs with thiol and triple bond functional groups. These surface-modified nanoparticles have a great potential to graft a variety of polymers with different molecular weights to its surface. Low molecular ATRP-synthesized poly (2-hydroxyethyl methacrylate) (PHEMA) as a hydrophilic polymer and polydopamine (PDA) as a hydrophobic one were synthesized and were covalently anchored to the surface of bi-functional SPIONs through double click reaction, i.e. [2 + 3] cycloaddition and thiol-ene reaction. As a result, polymeric Janus nanoparticles with amphiphilic and magnetic properties were obtained. The prepared polymers and SPIONs were fully characterized by various methods, as well as final polymeric Janus nanoparticles.

Bioevaluation of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with dihexadecyl phosphate (DHP)

Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for wide variety of applications. Their unique properties render them highly applicable as MRI contrast agents, in magnetic hyperthermia or targeted drug delivery. SPIONs surface properties affect a whole array of parameters such as: solubility, toxicity, stability, biodistribution etc. Therefore, progress in the field of SPIONs surface functionalization is crucial for further development of therapeutic or diagnostic agents. In this study, SPIONs were synthesized by thermal decomposition of iron (III) acetylacetonate Fe(acac)3 and functionalized with dihexadecyl phosphate (DHP) via phase transfer. Bioactivity of the SPION-DHP was assessed on SW1353 and TCam-2 cancer derived cell lines. The following test were conducted: cytotoxicity and proliferation assay, reactive oxygen species (ROS) assay, SPIONs uptake (via Iron Staining and ICP-MS), expression analysis of the following genes: alkaline phosphatase (ALPL); ferritin light chain (FTL); serine/threonine protein phosphatase 2A (PP2A); protein tyrosine phosphatase non-receptor type 11 (PTPN11); transferrin receptor 1 (TFRC) via RT-qPCR. SPION-DHP nanoparticles were successfully obtained and did not reveal significant cytotoxicity in the range of tested concentrations. ROS generation was elevated, however not correlated with the concentrations. Gene expression profile was slightly altered only in SW1353 cells.

Surface modification of super paramagnetic iron oxide nanoparticles via milk casein for potential use in biomedical areas

Super paramagnetic iron oxide nanoparticles (SPIONs) have proved that they have tremendous potential to use in various biomedical applications. But the surface of pure iron oxide nanoparticles so fast oxidized, that is a major drawback for biomedical applications. Covered SPIONs have good surface activity. Therefore, the first goal was to synthesize the naked SPIONs. Then we modified with 3-Aminopropyltriethoxysilane (APTES) and trichlorotriazine (TCT). Several techniques measurements were used for characterization the size and special features of naked SPIONs and TCT modified SPIONs. These results show that the SPIONs were synthesized. After that the SPIONs are coated with casein and indicate that there is an interaction between them. Moreover, we have investigated magnetic properties and anticancer effects of casein-coated SPIONs. Therefore, we showed casein could be used to increase the biocompatibility of the surface of SPIONs. At the end, we show that bonding of dipyridamole (DIP) to the surface of casein-coated SPIONs have good magnetite properties for targeted drug delivery. We find that the release of DIP by casein-coated SPIONs-DIP was sensitive to pH. Both release curves in pH 5.5 and 7.4 showed the release of DIP by β-casein coated SPIONs-DIP better than α-casein coated SPIONs-DIP. The cell culture studies of the casein-coated SPIONs-DIP provide good anticancer effects against both breast and prostate cancer cell lines. Here, we propose a simple and inexpensive chemical method for preparation of highly biocompatible core–shell SPIONs and binding of drug for using in targeted drug delivery system. Communicated by Ramaswamy H. Sarma

Beyond electrostatic interactions: Ligand shell modulated uptake of bis-conjugated iron oxide nanoparticles by cells

The effect of the ligand shell on the cellular uptake efficiency was evaluated by a systematic study using fully dispersed 6 nm diameter superparamagnetic iron oxide nanoparticles (SPIONs), mono and bis-conjugated with glycerol phosphate (glyc), dopamine (dopa), 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron) and phosphorylethanolamine (pea). Negatively charged SPION-glyc was more efficiently incorporated than positively charged SPION-pea and SPION-dopa clearly evidencing that there are strong enough short-range interactions in addition to the long-range electrostatic interactions, as measured by the zeta potential, to reverse our expectation on cellular uptake. Those effects were pursued by correlating the nanoparticles incorporation efficiency as a function of the respective zeta potentials and the molar fractions of glyc and pea ligands co-conjugated on the SPION surface. The possibility of associating different ligands to modulate the physicochemical properties and biological events was demonstrated, showing promising perspectives for the development of multifunctional nanosystems for biomedical applications.

Functionalized magnetic nanoparticles as chemosensors based on fluorene derivative for Cd(II) ions detection

Chemosensor of fluorene derivative (FL) contains different conjugated aromatic rings and binding sites that indicate the maximum fluorescence spectra at 505 nm in dimethylformamide solvation. The emission color is sensitive to changes in acidity and basicity solution which explain in twisted-intramolecular charge transfer and results in a sensitivity of metal ions. At neutral solution (pH 7), these molecules are sensitive to Cd(II) ions which illustrate red-shifted fluorescence spectra and the increase of Cd(II) ions concentration results in the increases of the fluorescence intensity. The limit of detection (LOD) of Cd(II) ions is 0.289 mg/L. The presence of other metal ions in Cd(II)-complexes shows the selectivity of Cd(II) ions and was not significantly sensitive to other metal ions. The carboxylic binding sites of FL chemosensor are important to interact with Cd(II) ions in dimethylformamide solvation and the cyano moiety can withdraw the charge transfer to binding site results in fluorescence intensity increasing. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) were used to improve signal fluorescence intensity for Cd(II) ions detection which lead to the lower limit of detection. The surface of SPIONs was modified with PMMA that it exhibits the decreased agglomeration of SPIONs. Then, the suspension of fluorescent magnetic nanoparticles was showed the good solubility in dimethylformamid when FL was coated on the PMMA/SPIONs.

Efficient Quantification by X-ray Photoelectron Spectroscopy and Thermogravimetric Analyses of the One-Pot Grafting of Two Molecules on the Surface of Iron Oxide Nanoparticles.

In this study, Superparamagnetic iron oxide nanoparticles (SPION) were functionalized in one pot with two organic molecules. Firstly, polyethylene glycol (PEG) was mixed for 46 hours to improve steric stability and then, two hours before the end of the reaction, dimercaptosuccinic acid (DMSA) was added to provide negative charges and thiol groups for post-functionalization. Three different molecular weights of PEG were used (550, 2000 and 5000 g mol-1). The main goal of this study was to characterize and quantify accurately the surface of SPION functionalized with two organic molecules. We demonstrated the advantages of coupling thermogravimetric and X-ray photoelectron spectrometry analyses to distinguish accurately the covering of SPION's surface. Thanks to the combination of these two techniques we were able to distinguish the amount of DMSA and PEG on SPION regarding the length of the polymer. We also showed that the length of the PEG influenced the quantity of DMSA adsorbed. With the smallest PEG (550 g mol-1) the presence of DMSA is almost ten times higher than with the two other PEG used proving that long polymers prevent the adsorption of small molecules on the surface of SPION.

Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy.

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.

Elaboration of Trans-Resveratrol Derivative-Loaded Superparamagnetic Iron Oxide Nanoparticles for Glioma Treatment.

In this work, new nanohybrids based on superparamagnetic iron oxide nanoparticles (SPIONs) were elaborated and discussed for the first time as nanovectors of a derivative molecule of trans-resveratrol (RSV), a natural antioxidant molecule, which can be useful for brain disease treatment. The derivative molecule was chemically synthesized (4’-hydroxy-4-(3-aminopropoxy) trans-stilbene: HAPtS) and then grafted onto SPIONs surface using an organosilane coupling agent, which is 3-chloropropyltriethoxysilane (CPTES) and based on nucleophilic substitution reactions. The amount of HAPtS loaded onto SPIONs surface was estimated by thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) analyses at 116 µmol·g−1 SPIONs. The synthesized HAPtS molecule, as well as the associated nanohybrids, were fully characterized by transmission electron microscopy (TEM), XPS, TGA, infrared (IR) and UV-visible spectroscopies, dynamic light scattering (DLS), and zeta potential measurements. The in vitro biological assessment of the synthesized nanohybrid’s efficiency was carried out on C6 glioma cells and showed that the nanovector SPIONs-CPTES-HAPtS do not affect the mitochondrial metabolism (MTT test), but damage the plasma membrane (FDA test), which could contribute to limiting the proliferation of cancerous cells (clonogenic test) at a HAPtS concentration of 50 µM. These nanoparticles have a potential cytotoxic effect that could be used to eliminate cancer cells.

Surface design and preparation of multi-functional magnetic nanoparticles for cancer cell targeting, therapy, and imaging.

Recently, theranostic candidates based on superparamagnetic iron oxide nanoparticles (SPIONs) providing the combination of therapy and diagnosis have become one of the most promising system in cancer research. However, poor stability, premature drug release, lack of specific tumor cell targeting, and complicated multi-step synthesis processes still hinder them for potential clinical applications. In this research, the multi-functional magnetic nanoparticles (MNPs-DOX) were prepared via a simple assembly process for targeted delivery of doxorubicin (DOX) and enhanced magnetic resonance (MR) imaging detection. Firstly, the multi-functional copolymer coating, polyamidoamine (PAMAM), was designed and synthesized by Michael addition reaction, where N,N-bis(acryloyl)cystamine served as backbone linker, and DOX, dopamine (DA), and polyethylene glycol (PEG) acted as comonomers. The PAMAM was then directly assembled to the surface of SPIONs by the ligand exchange reaction with SPIONs forming the MNPs-DOX. The hydrophilic PEG moieties provide the nanoparticles with colloidal stability and good-dispersity in aqueous solution. Comparing with the quick release of free DOX, the drug release behavior of MNPs-DOX exhibited a sustained drug release. Because the chemical cleavage of disulfide in the polymer backbone, a high cumulative drug release up to 60% in GSH within 48 h was observed, rather than only 26% in PBS (pH 7.4) without GSH. The MR imaging detection experiment showed that the MNPs-DOX had an enhanced T2 relaxivity of 126 mM−1 S−1 for MR imaging. The results of the cytotoxicity assays showed a remarkable killing effect of cancer cells by MNPs-DOX due to the FA tumor-targeting ligand, comparing with non-targeted drug molecules. All the results showed that the as prepared multi-functional magnetic nanoparticles may serve as a promising theranostic candidate for targeted anticancer drug delivery and efficient detection through MR imaging in medical application.

SPION@APTES@FA-PEG@Usnic Acid Bionanodrug for Cancer Therapy

In this work, we aimed to develop stable usnic acid (UA)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) as a potential drug carrier for in vitro analysis of MCF-7 (breast cancer cell line), HeLa (cervix cancer cell line), L929 (mouse fibroblast cell line), U87 (glioblastoma cell line, brain cancer), and A549 (human lung cancer cell line) cell lines. SPIONs were synthesized via the polyol method and functionalized with APTES using the Stober method. Carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and carboxylated luteolin (CL) were conjugated on the surface via a carboxylic/amine group using the nanoprecipitation method, respectively. X-ray powder diffraction analysis confirmed the purity of the product with crystallite size of around 11 nm. Fourier-transformed infrared spectrophotometer (FT-IR) analyses explained the conjugation of all functional groups to the surface of SPIONs. The percentages of inorganic and organic content in the products were investigated via thermal gravimetric analyzer (TGA). For morphological analysis, a transmission electron microscope (TEM) was used. The superparamagnetic property of the product was also confirmed by vibrating sample magnetometer (VSM).

Highly fluorescent and superparamagnetic nanosystem for biomedical applications

This work reports on highly fluorescent and superparamagnetic bimodal nanoparticles (BNPs) obtained by a simple and efficient method as probes for fluorescence analysis and/or contrast agents for MRI. These promising BNPs with small dimensions (ca. 17 nm) consist of superparamagnetic iron oxide nanoparticles (SPIONs) covalently bound with CdTe quantum dots (ca. 3 nm). The chemical structure of the magnetic part of BNPs is predominantly magnetite, with minor goethite and maghemite contributions, as shown by Mössbauer spectroscopy, which is compatible with the x-ray diffraction data. Their size evaluation by different techniques showed that the SPION derivatization process, in order to produce the BNPs, does not lead to a large size increase. The BNPs saturation magnetization, when corrected for the organic content of the sample, is ca. 68 emu g−1, which is only slightly reduced relative to the bare nanoparticles. This indicates that the SPION surface functionalization does not change considerably the magnetic properties. The BNP aqueous suspensions presented stability, high fluorescence, high relaxivity ratio (r2/r1 equal to 25) and labeled efficiently HeLa cells as can be seen by fluorescence analysis. These BNP properties point to their applications as fluorescent probes as well as negative T2-weighted MRI contrast agents. Moreover, their potential magnetic response could also be used for fast bioseparation applications.

Preparation of polydopamine based redox-sensitive magnetic nanoparticles for doxorubicin delivery and MRI detection

To improve the water-dispersity of superparamagnetic iron oxide nanoparticles (SPIONs), a novel polydopamine based redox-sensitive copolymer modified SPIONs were prepared for the biomedical application to deliver doxorubicin (DOX) and magnetic resonance imaging (MRI) detection. The major components of this nanoparticle include SPIONs and the redox-sensitive polydopamine (rPDA) crosslinked copolymer, where N,N-Bis(acryloyl) cystamine served as cross-linker, dopamine methacrylamide and a long-chain polyethylene glyco methyl ether methacrylate acted as comonomers. Here the rPDA@SPIONs were formed by the ligand exchange reaction of dopamine moiety with the oleic acid layer capped on the surface of SPIONs, and the inner area of the nanoparticles formed a reservoir for DOX, while the hydrophilic PEG moiety helped the nanoparticles well-dispersible in aqueous solution. The DOX-loaded rPDA@SPIONs demonstrated a high drug loading efficiency of 857 μg DOX per mg iron, and a strong T2 relaxivity of 123 mM^-1·S^-1 for MRI. The drug release analysis of drug-loaded nanoparticles showed a sustained and high cumulative drug release in GSH up to 73% within 48 h, rather than the relatively low release rate of 37% in PBS (pH 7.4) without GSH. All the results showed that the designed magnetic nanoparticle may be a promising vehicle for anticancer drug delivery with stimuli-triggered drug release behavior, and also a foundation for building smart theranostic formulations for efficient detection through MRI.

Superparamagnetic Iron Oxide Nanoparticles (SPION) Functionalized by Caffeic Acid (CFA)

In this research, we synthesized a novel caffeic acid-functionalized iron oxide nanoparticles (CFA-functionalized SPION) L929 (mouse fibroblast cell), U87 (glioblastoma brain cancer cell), MCF-7 (breast cancer cell), HeLa (cervix cancer cell), and A549 (human lung cancer cell) cell lines. Thermal decomposition and Stober methods were used to prepare APTES-capped SPION, respectively. The carboxylated polyethylene glycol (PEG-COOH), folic acid (FA), and caffeic acid (CFA) were attached to the surface of SPION via carboxylic/amine groups. Structural analysis (Rietveld analysis) confirmed the phase purity of the product. The conjugation of organics to the surface of SPION was followed with FT-IR spectroscopy and thermal gravimetric analysis (TGA). SEM analysis presented the spherical morphology of product with 13 ± 3 nm particle size. And also, superparamagnetic property of product was deduced from VSM analysis. Uptake of CFA-functionalized SPION from the cell and release of CFA from CFA-functionalized SPION has been studied by using Prussian blue staining and spectrophotometer, respectively. Also, cell viability and cytotoxicity was tested by MTT and LDH assays. The uptake of CFA-functionalized SPION by HeLa, MCF-7, and U87 was higher than A549 and L929 cells. Also, caffeic acid release from CFA-functionalized SPION increased at an acidic environment (pH 4.4). A newly synthesized CFA-functionalized SPION in all used concentrations decreased cell viability and increased cytotoxicity at 24th and 48th hours. The results showed that the CFA-functionalized SPION is a potential anticancer agent for cancer therapy.