Superparamagnetic Iron Oxide Nanocrystals Research Articles

Ultra-high capacity, multifunctional nanoscale sorbents for PFOA and PFOS treatment

Here, we describe surface functionalized, superparamagnetic iron oxide nanocrystals (IONCs) for ultra-high PFAS sorption and precise, low energy (magnetic) separation, considering perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). As a function of surface coating, sorption capacities described are considerably higher than previous studies using activated carbon, polymers, and unmodified metal/metal oxides, among others. In particular, positively charged polyethyleneimine (PEI) coated IONCs demonstrate extreme sorption capacities for both PFOA and PFOS due to electrostatic and hydrophobic interactions, along with high polymer grafting densities, while remaining stable in water, thus maintaining available surface area. Further, through a newly developed method using a quart crystal microbalance with dissipation (QCM-D), we present real-time, interfacial observations (e.g., sorption kinetics). Through this method, we explore underpinning mechanism(s) for differential PFAS (PFOA vs PFOS) sorption behavior(s), demonstrating that PFAS functional head group strongly influence molecular orientation on/at the sorbent interface. The effects of water chemistry, including pH, ionic composition of water, and natural organic matter on sorption behavior are also evaluated and along with material (treatment) demonstration via bench-scale column studies.

Superparamagnetic Nanocrystals Clustered Using Poly(ethylene glycol)-Crosslinked Amphiphilic Copolymers for the Diagnosis of Liver Cancer.

Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T2) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T2 relaxivity value 5.5 times higher than that of Resovist®. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.

SUPER-SENSITIVE REGISTRATION OF POLYFUNCTIONAL MAGNETIC NANOMATERIALS FOR THE RAPID DETERMINATION OF MOLECULAR MARKERS OF DISEASES

Magnetic particles (MPs) based on superparamagnetic iron oxide nanocrystals are increasingly used in modern research for the development of express technologies for high-precision determination of the concentration of biomolecules. In this work, we developed a universal method for using MPs as polyfunctional agents that perform several different functions in one analysis for topical issues of biochemical and medical diagnostics, based on the original technology of ultrasensitive detection of nonlinear magnetic nanomaterials. The method was tested for the rapid quantitative registration of cardiac markers and SARS-CoV-2-associated molecular markers in complex matrices. The proposed method is promising for creating test systems for prehospital monitoring, particularly for emergency molecular diagnostics in patients with suspected acute myocardial infarction, as well as for the rapid detection of coronavirus infection.

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer.

Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer's immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nano-drug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.

In situ self-assembly of amphiphilic dextran micelles and superparamagnetic iron oxide nanoparticle-loading as magnetic resonance imaging contrast agents.

Polymeric micelles have long been considered as promising nanocarrier for hydrophobic drugs and imaging probes, due to their nanoscale particle size, biocompatibility and ability to loading reasonable amount of cargoes. Herein, a facile method for dextran micelles preparation was developed and their performance as carriers of superparamagnetic iron oxide (SPIO) nanocrystals was evaluated. Amphiphilic dextran (Dex-g-OA) was synthesized via the Schiff base reactions between oxidized dextran and oleylamine, and self-assembled in situ into nano-size micelles in the reaction systems. The self-assembling behaviors of the amphiphilic dextran were identified using fluorescence resonance energy transfer technique by detection the energy transfer signal between the fluorophore pairs, Cy5 and Cy5.5. Hydrophobic SPIO nanoparticles (Fe3O4 NPs) were successfully loaded into the dextran micelles via the in situ self-assembly process, leading to a series of Fe3O4 NPs-loaded micelle nanocomposites (Fe3O4@Dex-g-OA) with good biocompatibility, superparamagnetism and strongly enhanced T 2 relaxivity. At the magnetic field of 0.5 T, the Fe3O4@Dex-g-OA nanocomposite with particle size of 116.2 ± 53.7 nm presented a higher T 2 relaxivity of 327.9 ·s-1. The prepared magnetic nanocomposites hold the promise to be used as contrast agents in magnetic resonance imaging.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T 1-T 2 dual-mode magnetic resonance imaging probes.

The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.

Hydrophobic Drug Release Studies from the Core/Shell Magnetic Mesoporous Silica Nanoparticles and their Anticancer Application

Multiple therapeutic hydrophobic drugs can be delivered simultaneously by inorganic, biocompatible iron core mesoporous silica shell nanoparticles. We synthesized superparamagnetic iron oxide nanocrystals encapsulated within mesostructured silica spheres through the sol-gel process. The dose of hydrophobic drugs Paclitaxel (PTX) and Camptothecin (CPT) loading and released on Fe3 O4 @SiO2 core/shell nanoparticle detected by U.V-visible spectrophotometry using a platform of nanoparticles (NPS). After being subjected to external heating, the drug release efficiency of paclitaxel (PTX) and camptothecin (CPT) Fe3 O4 @SiO2 core/shell nanoparticles is increased. Paclitaxel (PTX) and Camptothecin (CPT) Fe3 O4 @SiO2 core/shell nanoparticles did not heat the solution when an alternating magnetic field (AMF) was applied, and there was only mild drug leakage. When compared to Fe3 O4 @MSNs, the nanoparticles (PTX) and (CPT) Fe3 O4 @MSNs function as cancer-targeting mediators, increasing the killing of PANC-1 cancer cells. Human cancer cells were given these therapeutic anticancer water-insoluble drugs with nanoparticles, which is a valuable vehicle for drug delivery, and induced the inhibition of proliferation. Therefore, the goal of this study to emphasize Fe3 O4 @SiO2 core/shell potential as a superior candidate for hydrophobic drug delivery to the PANC-1 cancer cell.

Iron oxide-based enzyme mimic nanocomposite for dual-modality imaging guided chemical phototherapy and anti-tumor immunity against immune cold triple-negative breast cancer

Triple-negative breast cancer has few biomarkers to guide benefit from immunotherapy; furthermore, the biochemical features of the tumor microenvironment including acidosis, hypoxia, and high hydrogen peroxide concentrations, significantly modulate cancer cell metabolism and metastatic potential, and associate with bad outcomes from chemo-radiotherapy and surgery. Herein, a theranostic nanocomposite with a dual imaging modality and chemical phototherapeutic capacity has been used for breast cancer cell inhibition, which is developed to self-assemble superparamagnetic iron oxide nanocrystals and IR-780 iodides in one system. Due to the magnetic resonance and near-infrared Ⅱ fluorescence capacity, this nanocomposite serves as a contrast agent for the high-sensitivity, accurate cancer diagnosis and facilitates imaging-guided phototherapy. Furthermore, this nanocomposite not only performs dual enzyme-like activities in the tumor microenvironment, but also carries out the bioeffect of hyperthermia and oxidative stress, which could repolarize tumor-associated macrophages from the tumor-promoting M2 phenotype into the tumoricidal M1 phenotype, reduce the number of immunosuppressive cells, and execute immune activation. Through simultaneous chemical phototherapy and anti-tumor immunity, this iron oxide-based nanocomposite successfully suppresses tumor growth and metastasis, and has good biocompatibility in normal tissues and organs; thus, it might provide new insights into the development of a novel cancer therapy strategy.

Effect of Fe₃O₄ Nanomaterial-Based MRI on the Efficacy of One-Sided Butterfly Sinus Lesions in the Nose.

Fe₃O₄ materials have many crystal forms, and the morphology of their nanomaterials is more diverse. Under the influence of nano-effects, they exhibit unique physical and chemical properties. The synthesized Fe₃O₄ materials with different morphologies have different properties. They are widely used in related fields such as electromagnetics, chemical engineering, catalysis, sensors, acoustics, medicine, environmental protection and so on. Choosing the appropriate contrast agent to display the anatomical characteristics of diseased and normal tissue is an important thing before using MRI (Magnetic Resonance Imaging) technology. At present, Gd-DTPA is a commonly used magnetic contrast agent in clinical practice, but Gd-DTPA has obvious shortcomings, such as short circulation time, non-specific distribution, and high price. In comparison, the superparamagnetic iron oxide nanocrystals have a high specific distribution in living tissues, mainly concentrated in reticular endothelial cells-rich tissues and organs, such as liver, spleen, lymph nodes and bone marrow. This study analyzed the imaging characteristics of 21 patients with unilateral benign sphenoid sinus disease who were confirmed by nasal endoscopic surgery and postoperative pathology. Among the 21 patients with unilateral benign sphenoid sinus lesions, 7 cases of them had cysts. Those with altered sphenoid sinus cavity expansion may be accompanied by thinning of bone resorption. MRI manifested as long T1 and long T₂ irregular spherical signal shadows. 8 cases of them are fungal lesions. MRI showed mixed signals are in the sphenoid sinus, the flaky exudation showed a high signal, and the fungal nodule showed a low T₂WI signal. In the 3 cases of cerebrospinal fluid rhinorrhea, MRI showed a line between the high-signal shadow of the cerebrospinal fluid and the high-signal liquid shadow in the sinuses. High signal and shadow are connected, and other tissues (brain tissue, nasal mucosa) show low signal. Fe₃O₄-based MRI technology can improve imaging quality and diagnostic efficiency.

Mn(ii) chelate-coated superparamagnetic iron oxide nanocrystals as high-efficiency magnetic resonance imaging contrast agents.

In this communication, a paramagnetic bifunctional manganese(ii) chelate ([Mn(Dopa-EDTA)]2−) containing a catechol group is designed and synthesized. The catechol can bind iron ions on the surface of superparamagnetic iron oxide (SPIO) nanocrystals to form core–shell nanoparticles. Both 4 and 7 nm SPIO@[Mn(Dopa-EDTA)]2− show good water solubility, single-crystal dispersion, and low cytotoxicity. The study of the interplay between the longitudinal and transverse relaxation revealed that 4 nm SPIO@[Mn(Dopa-EDTA)]2− with lower r2/r1 = 1.75 at 0.5 T tends to be a perfect T1 contrast agent while 7 nm SPIO@[Mn(Dopa-EDTA)]2− with a higher r2/r1 = 15.0 at 3.0 T tends to be a T2 contrast agent. Interestingly, 4 nm SPIO@[Mn(Dopa-EDTA)]2− with an intermediate value of r2/r1 = 5.26 at 3.0 T could act as T1–T2 dual-modal contrast agent. In vivo imaging with the 4 nm SPIO@[Mn(Dopa-EDTA)]2− nanoparticle shows unique imaging features: (1) long-acting vascular imaging and different signal intensity changes between the liver parenchyma and blood vessels with the CEMRA sequence; (2) the synergistic contrast enhancement of hepatic imaging with the T1WI and T2WI sequence. In summary, these Fe/Mn hybrid core–shell nanoparticles, with their ease of synthesis, good biocompatibility, and synergistic contrast enhancement ability, may provide a useful method for tissue and vascular MR imaging.

Design Principles for Thermoresponsive Core-Shell Nanoparticles: Controlling Thermal Transitions by Brush Morphology.

In this feature article, we summarize our recent work on understanding and controlling the thermal behavior of nanoparticles grafted with thermoresponsive polymer shells. Precision synthesis of monodisperse superparamagnetic iron oxide nanocrystals was combined with irreversible dense grafting of nitrodopamide-anchored thermoresponsive polymer chains. We provide an overview of how the dense and stable grafting of biomedically relevant polymers, including poly(ethylene glycol), poly(N-isopropylacrylamide), polysarcosin, and polyoxazolines, can be achieved. This platform has made it possible for us to demonstrate that the polymer brush geometry, as defined by the nanoparticle core and relative polymer brush size, determines the thermal transitions of the polymer brush. We furthermore summarize our work on how the polymer shell transitions and nanoparticle aggregation can be tuned. With the independent variation of the core and the shell, we can optimize and precisely control the thermally controlled solubility of our system. Finally, our feature article gives examples relevant to current and future applications. We show how the thermal response of the shell influences the nanoparticle performance in biological fluids and interactions with proteins and cells, also under purely magnetic actuation of the nanoparticles through the superparamagnetic iron oxide core.

Synthesis and characterization of magnetic dextran nanogel doped with iron oxide nanoparticles as magnetic resonance imaging probe.

Magnetic hybrid nanogels composed of magnetic nanoparticles and polymer hydrogel matrix have drawn much attention because of their unique superparamagnetic properties and biocompatibility as biomaterials. In this study, a facile method was developed for the preparation of iron oxide nanoparticle-loaded magnetic dextran nanogel as magnetic resonance imaging (MRI) probe. Water soluble superparamagnetic iron oxide nanocrystals (Fe3O4) was pre-synthesized and physically doped into a Schiff base-containing dextran nanogel formed using W/O microemulsion as nanoreactor. Magnetic dextran nanogel (Fe3O4@Dex) with particle size of 300-1000 nm was obtained with multiple Fe3O4 nanoparticles randomly encapsulated in the hydrogel networks. Magnetization and T2 relaxivity study shows that the resulted magnetic nanogel has similar superparamagneitc behaviors with single Fe3O4 nanocrystals, and relatively higher T2 relaxivity (277.2 mMFe-1·s-1) as MRI probe. Notably, Schiff base linkages and aldehyde groups on the dextran hydrogel matrix endow the magnetic nanogel with pH-sensitiveness and reactive groups for further modifications, which make the magnetic dextran nanogel a promising nanoplatform as MRI-guided drug delivery system with acid environment-responsiveness.

Chemistry of Shape-Controlled Iron Oxide Nanocrystal Formation.

Herein, we demonstrate that meticulous and in-depth analysis of the reaction mechanisms of nanoparticle formation is rewarded by full control of the size, shape, and crystal structure of superparamagnetic iron oxide nanocrystals during synthesis. Starting from two iron sources, iron(II) and iron(III) carbonate, a strict separation of oleate formation from the generation of reactive pyrolysis products and concomitant nucleation of iron oxide nanoparticles was achieved. This protocol enabled us to analyze each step of nanoparticle formation independently in depth. The progress of the entire reaction was monitored via matrix-assisted laser desorption ionization time-of-flight mass spectrometry and gas chromatography, thus providing insight into the formation of various iron oleate species prior to nucleation. Interestingly, due to the intrinsic strongly reductive pyrolysis conditions of the oleate intermediates and redox process in early stages of the synthesis, pristine iron oxide nuclei were composed exclusively from wüstite irrespective of the oxidation state of the iron source. Controlling the reaction conditions provided a very broad range of size- and shape-defined monodispersed iron oxide nanoparticles. Curiously, after nucleation, star-shaped nanocrystals were obtained that underwent metamorphism toward cubic-shaped particles. Electron energy loss spectroscopy tomography revealed ex post oxidation of the primary wustite nanocrystal, providing a full 3D image of Fe2+ and Fe3+ distribution within. Overall, we developed a highly flexible synthesis, yielding multi-gram amounts of well-defined iron oxide nanocrystals of different sizes and morphologies.

The Regulation of Mesenchymal Stem Cell Therapy Through Magnetic Resonance Imaging Agents-Based Cellular Condition and Oxygen Environment.

Repairing articular cartilage defects is difficult due to the hypovascular biostructure and poor self-repairing capacity of articular cartilage. Currently, mesenchymal stem cells (MSCs) with excellent differentiation potential are considered as a promising biological approach for cartilage regeneration. The effect, however, remains far from satisfactory for clinical applications owing to the main drawbacks of tracking the retention of cells and a low differentiation efficiency. As known, the nanoparticles with superparamagnetic properties has been used to monitor the MSCs in vivo through magnetic resonance imaging (MRI) in clinical application. In this study, different external and internal bio-conditions were applied to regulate the biological behavior of cells. Here, intracellular MRI contrast agents, superparamagnetic iron oxide nanocrystals (SPIONs), and a hypoxic culture environment were found to exert synergistic effects on gene and protein expression, and the cell viability, cell cycle, apoptosis, reactive oxygen species and the stem cell differentiations were measured. The levels of chondrogenic and migrant markers (including collagen II, collagen X, aggrecan, SOX9, MMPs and CXCR4) increased, triggering directional differentiation and enhancing cell migration to the inflammatory site. Moreover, SPION-labeled hypoxia-preconditioned MSCs were found without reactive oxygen species generation and transplanted into rat models with articular cartilage disorders. Interestingly, MRI and histological identification confirmed that new cartilage-like tissue was regenerated and that defects were repaired, and this method is more efficient for cartilage regeneration than SPION-labeled normoxia MSCs. The synergistic effect of hypoxia-precondition and SPIONs based cellular iron source could improve the cell migration and facilitate chondrogenic differentiation.

Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy

There exists an urgent medical demand at present to develop therapeutic strategies which can improve the treatment outcome of hepatocellular carcinoma (HCC). Here, we explore the biological functions and clinical significance of PBOV1 in HCC in order to push forward the diagnosis and treatment of HCC. Using theranostical nanomedicines, PBOV1 is verified to be a key oncogene which greatly promotes HCC proliferation, epithelial-to-mesenchymal transition, and stemness by activating the Wnt/β-catenin signaling pathway. Therefore, single-chain antibody for epidermal growth factor receptor (scAb-EGFR)-targeted nanomedicine effectively silencing the PBOV1 gene exhibits potent anticancer effects. In vivo HCC-targeting siRNA delivery mediated by the theranostical nanomedicine remarkably inhibits the tumor growth and metastasis. In addition, the superparamagnetic iron oxide nanocrystals (SPION)-encapsulated nanomedicines possess high MRI detection sensitivity, which endows them with the potential for MRI diagnosis of HCC. This study shows that PBOV1 represents a prognostic biomarker and therapeutic target for HCC.

One-pot synthesis of maghemite nanocrystals across aqueous and organic solvents for magnetic hyperthermia

Superparamagnetic iron oxide nanocrystals (SPIONs) continue to receive intensive interest due to their significant prospects in biomedical applications. However, a critical requirement for such applications is the ability to synthesise high quality nanocrystals that are not only readily dispersible in aqueous solvents, but also retain good magnetic properties in an aqueous medium. This is not easy to achieve because, although organic solvent-based syntheses provide better control over SPIONs properties, their magnetic properties in particular, tend to deteriorate during aqueous phase transfer. In the current work, we propose a new route for the synthesis of high quality SPIONs using triethylamine (TEA) as a dynamic amphiphilic molecule. We demonstrate that in a single step, TEA can directly synthesise SPIONs that are readily dispersible in both aqueous and organic media. We further demonstrate the versatility of TEA in facilitating one-step phase transfer of SPIONs from organic to aqueous solvents. We then extend the applicability of this approach to demonstrate for the first time that organic molecules-capped SPIONs can also be directly dispersed in aqueous solvents. These SPIONs show remarkable potential for hyperthermia, as demonstrated through their outstanding magnetic field induced heating performance, which improves after their phase transfer to the aqueous phase. The current study establishes the importance of a suitable nanoparticle phase transfer protocol to ensure that the final product retains all the desirable application-focussed properties.

Paclitaxel-induced formation of 3D nanocrystal superlattices within injectable protein-based hybrid nanoparticles.

Self-assembly of monodisperse superparamagnetic iron oxide nanocrystals into a close-packed, three-dimensional (3D) superlattice is designed within cross-linked protein-based nanoparticles composed of human serum albumin and polyethylene glycol. The prepared nanoparticles are very stable in serum and exhibit a high T2 relaxivity as well as anti-cancer activity, indicating the practical benefits of ordering nanocrystals.

Design and Fabrication of Magnetically Responsive Nanocarriers for Drug Delivery.

Magnetically-assisted delivery of therapeutic agents to the site of interest, which is referred to as magnetic drug targeting, has proven to be a promising strategy in a number of studies. One of the key advantages over other targeting strategies is the possibility to control remotely the distribution and accumulation of the nanocarriers after parenteral administration. However, preparation of effective and robust magnetically responsive nanocarriers based on superparamagnetic iron oxide nanocrystals (SPIONs) still represents a great scientific challenge, since spatial guidance of individual SPIONs is ineffective despite the presence of high magnetic field gradient. A strategy to overcome this issue is the clustering of SPIONs to achieve sufficient magnetic responsiveness. In this mini-review, we address current and future strategies for the design and fabrication of magnetically responsive nanocarriers based on SPIONs for magnetically-targeted drug delivery, including the underlying physical requirements, the possibility of drug loading, and the control of drug release at the targeted site.

Nanocomposites of Highly Monodisperse Encapsulated Superparamagnetic Iron Oxide Nanocrystals Homogeneously Dispersed in a Poly(ethylene Oxide) Melt.

Nanocomposite materials based on highly stable encapsulated superparamagnetic iron oxide nanocrystals (SPIONs) were synthesized and characterized by scattering methods and transmission electron microscopy (TEM). The combination of advanced synthesis and encapsulation techniques using different diblock copolymers and the thiol-ene click reaction for cross-linking the polymeric shell results in uniform hybrid SPIONs homogeneously dispersed in a poly(ethylene oxide) matrix. Small-angle X-ray scattering and TEM investigations demonstrate the presence of mostly single particles and a negligible amount of dyads. Consequently, an efficient control over the encapsulation and synthetic conditions is of paramount importance to minimize the fraction of agglomerates and to obtain uniform hybrid nanomaterials.

Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo.

Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min. Furthermore, accumulation of the coated particles was mainly taking place in the spleen whereas uncoated nanoparticles were rapidly deposited in the liver. The protein coronas of the particles differed considerably from each other. The uncoated particles had substantially more proteins adsorbed including liver and immune active proteins, whereas the coated particles had proteins capable of suppressing cellular uptake. These reasons along with agglomeration observed in blood circulation were concluded to cause the differences in the behavior in vivo. The biofate of the particles was monitored with magnetic resonance imaging by incorporating superparamagnetic iron oxide nanocrystals inside the pores of the particles making dynamic imaging of the particles feasible. The results of the present study pave the way for further development of the porous inorganic delivery system in the sense of active targeting as the carriers can be easily chemically modified allowing also magnetically targeted delivery and diagnostics.