Efficient delivery of anticancer drugs using functionalized-Ag-decorated Fe3O4@SiO2 nanocarrier with folic acid and ß-cyclodextrin.

Nanocarrier surface functionalization has been widely regarded as a promising approach for achieving precise and targeted drug delivery systems. In this work, the fabrication of functionalized-Ag-decorated Fe3O4@SiO2 (Fe3O4@SiO2-Ag) nanocarriers with folic acid (FA) and ß-cyclodextrin (BCD) exhibit a remarkable capacity for delivering two types of anticancer drugs, i.e., doxorubicin (DOX) and epirubicin (EPI), into cancer cells. The effective functionalization of Fe3O4@SiO2-Ag nanoparticles has been achieved through the use of cysteine (Cys) as an anchor for attaching FA and BCD via EDC-NHS coupling and Steglich esterification methods, respectively. The findings indicate that surface functionalization had no significant impact on the physicochemical characteristics of the nanoparticles. However, it notably affected DOX and EPI loading and release efficiency. The electrostatic conjugation of DOX/EPI onto the surface of Fe3O4@SiO2-Ag/Cys/FA and Fe3O4@SiO2-Ag/Cys/BCD exhibited maximum loading efficiency of 50-60% at concentration ratio of DOX/EPI to nanoparticles of 1:14. These nanocarriers also achieved an 40-47% DOX/EPI release over 36 days. Furthermore, the drug-loaded functionalized-nanocarrier showed cytotoxic effects on SK-MEL-2 cells, as demonstrated by an in vitro MTT assay. This suggests that the as-prepared functionalized-nanoparticles have promise as a carrier for the efficient anticancer drugs.

Acoustic-responsive carbon dioxide-loaded liposomes for efficient drug release.

The role of liposomes as drug carriers has been investigated. Ultrasound-based drug release methods have been developed for on-demand drug delivery. However, the acoustic responses of current liposome carriers result in low drug release efficiency. In this study, CO2-loaded liposomes were synthesized under high pressure from supercritical CO2 and irradiated with ultrasound at 237 kHz to demonstrate their superior acoustic responsiveness. When liposomes containing fluorescent drug models were irradiated with ultrasound under acoustic pressure conditions that are safe for the human body, CO2-loaded liposomes synthesized using supercritical CO2 had 17.1 times higher release efficiency than liposomes synthesized using the conventional Bangham method. In particular, the release efficiency of CO2-loaded liposomes synthesized using supercritical CO2 and monoethanolamine was 19.8 times higher than liposomes synthesized using the conventional Bangham method. These findings on the release efficiency of acoustic-responsive liposomes suggest an alternative liposome synthesis strategy for on-demand release of drugs by ultrasound irradiation in future therapies.

Levilactobacillus brevis surface layer protein B promotes liposome targeting to antigen-presenting cells in Peyer's patches.

Liposome targeting by conjugation with specific ligands and cross-linking reagents is an attractive strategy for active drug delivery. Here, we demonstrated the potential of surface layer protein (Slp) B from Levilactobacillus brevis JCM 1059 as a specific ligand to antigen-presenting cells (APCs) in Peyer's patches. L. brevis JCM 1059 SlpB-coated liposomes (SlpB-LPs) showed higher resistance to various pH values and bile acids compared to non-coated liposomes (LPs). SlpB-LP showed a significantly higher uptake into dendritic cell-like differentiated THP-1 cells than LP did. The SlpB-LP-conjugated α-galactosylceramide (αGalCer) promoted the production of IL-12 (p40) and TNF-α by THP-1 cells. Furthermore, SlpB-LP showed significantly higher delivery efficiency into APCs underlaying microfold (M) cells in Peyer's patches after oral administration in BALB/c mice and enhanced IL-12 production when αGalCer was conjugated to SlpB-LP. In conclusion, the present study demonstrates the therapeutic potential of SlpB-coated LP to deliver immunomodulatory components to the gut immune system.

Bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers for efficient targeted anticancer drug delivery.

Functionalization of nanocarriers has been considered the most promising way of ensuring an accurate and targeted drug delivery system. This study reports the synthesis of bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers with an excellent ability to deliver doxorubicin (DOX), an anticancer drug, into the intercellular matrix. Here, the presence of amine and carboxylate groups enables aspartic acid (AA) to be used as an efficient anchoring molecule for the conjugation of folic acid (FA) (EDC-NHS coupling) and DOX (electrostatic interaction). Based on the results, surface functionalization showed little effect on the physicochemical properties of the nanoparticles but significantly influenced both the loading and release efficiency of DOX. This is primarily caused by the steric hindrance effect due to large and bulky FA molecules. Furthermore, in vitro MTT assay of B16-F1 cell lines revealed that FA conjugation was responsible for a significant increase in the cytotoxicity of DOX-loaded nanocarriers, which was also found to be proportional to AA concentration. This high cytotoxicity resulted from an efficient cellular uptake induced by the over-expressed folate receptors and fast pH triggered DOX release inside the target cell. Here, the lowest IC50 value of DOX-loaded nanocarriers was achieved at 2.814 ± 0.449 µg mL-1. Besides, further investigation also showed that the drug-loaded nanocarriers exhibited less or no toxicity against normal cells.

Quantitative Analysis of Acoustic Pressure for Sonophoresis and Its Effect on Transdermal Penetration.

Ultrasound facilitates the penetration of macromolecular compounds through the skin and offers a promising non-invasive technique for transdermal delivery. However, technical difficulties in quantifying ultrasound-related parameters have restricted further analysis of the sonophoresis mechanism. In this study, we devise a bolt-clamped Langevin transducer-based sonophoresis device that enables us to measure with a thin lead zirconate titanate (PZT) sensor. One-dimensional acoustic theory accounting for wave interaction at the skin interface indicates that the acoustic pressure and cavitation onset on the skin during sonophoresis are sensitive to the subcutaneous support, meaning that there is a strong need to perform the pressure measurement in an experimental environment replacing the human body. From a series of the experiments with our new device, the transdermal penetration of polystyrene, silica and gold nanoparticles is found to depend on the size and material of the particles, as well as the hardness of the subcutaneous support material. We speculate from the acoustic pressure measurement that the particles' penetration results from the mechanical action of cavitation.

Fabrication of porous FePt microcapsules for immunosensing techniques.

Porous FePt microcapsules are fabricated for use in bead-based immunoassay technologies, that generally use magnetic spheres to immobilize biomolecules on their surface. The magnetic capsules can be used to carry assay reagents to reduce the time required to perform immunoassay processes, and microsize capsules are easier to manipulate magnetically than nanosize ones. Silica particles of approximately 2.5 µm diameter are used as templates and modified with poly(ethyleneimine) (PEI), which enables FePt nanoparticles to accumulate selectively on the template particles and an FePt shell to be formed by a polyol process. To increase the mechanical stability of the FePt nanoparticle assembly shell, a double-layered FePt nanoparticle assembly is fabricated by repeating the modification process of PEI and the synthesis process of FePt nanoparticles, resulting in the fabrication of magnetic capsules with a three-dimensional structure. We further investigate the ability of magnetic capsules to immobilize antibodies on their surface. Gold nanoparticles are used as linkers between the magnetic microcapsules and antibodies. The antibodies are successfully immobilized on the surface of the developed microsize FePt capsules.

Size-tunable drug-delivery capsules composed of a magnetic nanoshell.

Nano-sized FePt capsules with two types of ultrathin shell were fabricated using a template method for use in a nano-scale drug delivery system. One capsule was composed of an inorganic-organic hybrid shell of a water-soluble polymer and FePt nanoparticles, and the other capsule was composed of a network of fused FePt nanoparticles. We demonstrated that FePt nanoparticles selectively accumulated on the polymer molecules adsorbed on the template silica particles, and investigated the morphologies of the particle accumulation by changing the concentration of the polymer solution with which the template particles were treated. Capsular size was reduced from 340 to less than 90 nm by changing the size of the silica template particles, and the shell thickness was controlled by changing the amount of FePt nanoparticles adsorbed on the template particles. The hybrid shell was maintained by the connection of FePt nanoparticles and polymer molecules, and the shell thickness was 10 nm at the maximum. The FePt network shell was fabricated by hydrothermal treatment of the FePt/polymer-modified silica composite particles. The FePt network shell was produced from only the FePt alloy, and the shell thickness was 3 nm. Water-soluble anti-cancer drugs could be loaded into the hollow space of FePt network capsules, and lipid-coated FePt network capsules loaded with anti-cancer drugs showed cellular toxicity. The nano-sized capsular structure and the ultrathin shell suggest applicability as a drug carrier in magnetically guided drug delivery systems.

A magnetically guided anti-cancer drug delivery system using porous FePt capsules.

Magnetic carriers with efficient loading, delivery, and release of drugs are required for magnetically guided drug delivery system (DDS) as the potential cancer therapy. The present article describes the fabrication of porous FePt capsules approximately 340 nm in diameter with large pores of 20 nm in an ultrathin shell of 10 nm and demonstrates their application to a magnetically guided DDS in vitro. An aqueous anti-cancer drug is easily introduced in the hollow space of the capsules without external stimuli and released to cancer cells on cue through the magnetic shell composed of an ordered-alloy FePt network structure, which exhibits superparamagnetic features at approximately body temperature. The drug-loaded magnetic capsules coated with a lipid membrane are efficiently guided to the cancer cells within 15 min using a NdFeB magnet (0.2 T), and more than 70% of the cancer cells are destroyed.

Inorganic-organic magnetic nanocomposites for use in preventive medicine: a rapid and reliable elimination system for cesium.

PURPOSE: To investigate the potential use of Prussian blue-coated magnetic nanoparticles, termed "Prussian blueberry", to bring about the magnetic elimination of cesium. METHODS: Prussian blueberry were prepared by a layer-by-layer assembly method. The morphology, structure and physical properties of the Prussian blueberry were investigated as was their ability to magnetically eliminate cesium. RESULTS: We confirmed that Prussian blueberry were composed of a magnetite nanoparticle-core and a Prussian blue-shell. Under a magnetic field, Prussian blueberry (5 mg) reduced the cesium concentration of seawater (3 ml) from 150 ppm to about 50 ppm; but regular Prussian blue could not magnetically eliminate cesium. Moreover, Prussian blueberry removed a similar proportion of cesium from a larger volume of seawater, and from fetal bovine serum and cow's milk. CONCLUSIONS: Under a magnetic field, Prussian blueberry was able to rapidly eliminate cesium from seawater and from biological matrices such as serum and milk.

Nanomedicine for cancer: lipid-based nanostructures for drug delivery and monitoring.

Recent advances in nanotechnology, materials science, and biotechnology have led to innovations in the field of nanomedicine. Improvements in the diagnosis and treatment of cancer are urgently needed, and it may now be possible to achieve marked improvements in both of these areas using nanomedicine. Lipid-coated nanoparticles containing diagnostic or therapeutic agents have been developed and studied for biomedical applications and provide a nanomedicine strategy with great potential. Lipid nanoparticles have cationic headgroups on their surfaces that bind anionic nucleic acids and contain hydrophobic drugs at the lipid membrane and hydrophilic drugs inside the hollow space in the interior. Moreover, researchers can design nanoparticles to work in combination with external stimuli such as magnetic field, light, and ionizing radiation, which adds further utility in biomedical applications. In this Account, we review several examples of lipid-based nanoparticles and describe their potential for cancer treatment and diagnosis. (1) The development of a lipid-based nanoparticle that included a promoter-enhancer and transcriptional activator greatly improved gene therapy. (2) The addition of a radiosensitive promoter to lipid nanoparticles was sufficient to confer radioisotope-activated expression of the genes delivered by the nanoparticles. (3) We successfully tailored lipid nanoparticle composition to increase gene transduction in scirrhous gastric cancer cells. (4) When lipophilic photosensitizing molecules were incorporated into lipid nanoparticles, those particles showed an increased photodynamic cytotoxic effect on the target cancer. (5) Coating an Fe(3)O(4) nanocrystal with lipids proved to be an efficient strategy for magnetically guided gene-silencing in tumor tissues. (6) An Fe(16)N(2)/lipid nanocomposite displayed effective magnetism and gene delivery in cancer cells. (7) Lipid-coated magnetic hollow capsules carried aqueous anticancer drugs and delivered them in response to a magnetic field. (8) Fluorescent lipid-coated and antibody-conjugated magnetic nanoparticles detected cancer-associated antigen in a microfluidic channel. We believe that the continuing development of lipid-based nanomedicine will lead to the sensitive minimally invasive treatment of cancer. Moreover, the fusion of different scientific fields is accelerating these developments, and we expect these interdisciplinary efforts to have considerable ripple effects on various fields of research.

Ferromagnetic FePt-nanoparticles/polycation hybrid capsules designed for a magnetically guided drug delivery system.

The present Article describes the synthesis of ferromagnetic capsules approximately 330 nm in diameter with a nanometer-thick shell to apply to magnetic carriers in a magnetically guided drug delivery system. The magnetic shell of 5 nm in thickness is a nanohybrid, composed of ordered alloy FePt nanoparticles of approximately 3-4 nm in size and a polymer layer of a cationic polyelectrolyte, poly(diaryldimethylammonium chloride) (PDDA). The magnetic capsules have an excellent capacity for carrying medical drugs and genes. Surface-modified silica particles with PDDA were used as a template for the capsules. FePt nanoparticles were deposited on the PDDA-modified silica particles through a polyol method followed by dissolving the silica particles with a NaOH solution, resulting in the formation of the magnetic capsules as the final product. A three-dimensional hollow structure is maintained by the nanohybrid shell. The FePt-nanoparticles/PDDA nanohybrid shell also exhibits a ferromagnetic feature at room temperature because the FePt nanoparticles of an ordered-alloy phase are formed with the aid of PDDA despite the small size (3-4 nm).

Direct synthesis of fct-structured FePt nanoparticles at low temperature with assistance of poly(N-vinyl-2-pyrrolidone).

Direct synthesis of fct-structured FePt nanoparticles was successfully achieved by using poly(N-vinyl-2-pyrrolidone) as a protective reagent at lower temperature than the case using low molecular weight ligands as a protective reagent. Experimental data suggest that a transformation of FePt nanoparticles from face-centered cubic to face-centered tetragonal (fct) structure takes place at reaction temperature of 261 degrees C. The results of XRD and the magnetic properties exhibit that the FePt nanoparticles synthesized at 261 degrees C have partially ordered fct-structure and a ferromagnetic behavior at room temperature.