Theranostic Role of Iron Oxide Nanoparticle for Treating Renal Anemia: Evidence of Efficacy and Significance by MRI, Histology and Biomarkers.

(1) Background: Increasing attention has been given to applying nanosized iron oxide nanoparticles (IOPs) to treat iron deficiency anemia (IDA). Chronic kidney disease (CKD) patients who suffer from IDA often need long-term iron supplements. We aim to evaluate the safety and therapeutic effect of MPB-1523, a novel IOPs, in anemic CKD mice and to monitor iron storage by magnetic resonance (MR) imaging.

IOP Injection, A Novel Superparamagnetic Iron Oxide Particle MRI Contrast Agent for the Detection of Hepatocellular Carcinoma: A Phase II Clinical Trial.

Background: MRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver-specific contrast agents which enhance lesions in T -weighted images. Iron oxide nano-particle m-PEG-silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial.

Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis.

Purpose: The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo.

Procedures: Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide.

Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.

In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis.

Targeting microbubbles-carrying TGFβ1 inhibitor combined with ultrasound sonication induce BBB/BTB disruption to enhance nanomedicine treatment for brain tumors.

The clinical application of chemotherapy for brain cancer tumors remains a challenge due to difficulties in the transport of therapeutic agents across the blood-brain barrier/blood-tumor barrier (BBB/BTB). In this study, we developed des-octanoyl ghrelin-conjugated microbubbles (GMB) loaded with TGFβ1 inhibitor (LY364947) (GMBL) to induce BBB/BTB disruption for ultrasound (US) sonication with GMBL. The in-vitro stability study showed that GMB was pretty stable over one month.

Development of a diagnostic polymersome system for potential imaging delivery.

In order to enhance visualization of soft tissues, a dual-imaging diagnostic polymersome system featured with highly hydrated multilamellar wall structure capable of simultaneously embedding a hydrophobic near-infrared fluorophore, Cy5.5, and a paramagnetic probe, gadolinium (Gd(III)) cations was developed. The polymersomes were obtained from the self-assembly of lipid-containing copolymer, poly(acrylic acid-co-distearin acrylate), in aqueous solution.

Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system.

Chemotherapy for brain cancer tumors remains a big challenge for clinical medicine due to the inability to transport sufficient drug across the blood-brain barrier (BBB) and the poor penetration of drug into the tumors. To effectively treat brain tumors and reduce side effects on normal tissues, both des-octanoyl ghrelin and folate conjugated with polymersomal doxorubicin (GFP-D) was developed in this study to help transport across the BBB and target the tumor as well. The size measurements revealed that this BBB-penetrating cancer cell-targeting GFP-D was about 85 nm.

Drug delivery system design and development for boron neutron capture therapy on cancer treatment.

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,l-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content.

Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues.

The effective protection of the blood-brain barrier (BBB) from tight junctions and efflux transport systems ultimately results in the limited entry of 95% of drug/gene candidates, which are potentially beneficial for central nervous system (CNS) diseases. In order to enhance the brain-specific delivery, in this study we developed a targeting carrier system, which consists of poly(carboxyl ethylene glycol-g-glutamate)-co-poly(distearin-g-glutamate) (CPEGGM-PDSGM) polymersomes with the conjugation of des-octanoyl ghrelin. Des-octanoyl ghrelin across the BBB was reported to be unidirectional (blood-to-brain direction).

In vitro evaluation of the L-peptide modified magnetic lipid nanoparticles as targeted magnetic resonance imaging contrast agent for the nasopharyngeal cancer.

The purpose of this study was to analyze the encapsulation of superparamagnetic iron oxide nanoparticles (SPION) by the lipid nanoparticle conjugated with the 12-mer peptides (RLLDTNRPLLPY, L-peptide), and the delivery of this complex into living cells. The lipid nanoparticles employed in this work were highly hydrophilic, stable, and contained poly(ethylene-glycol) for conjugation to the bioactive L-peptide. The particle sizes of two different magnetic lipid nanoparticles, L-peptide modified (LML) and non-L-peptide modified (ML), were both around 170 nm with a narrow range of size disparity.

Improved photodynamic cancer treatment by folate-conjugated polymeric micelles in a KB xenografted animal model.

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta-tetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed.

Tracking T-cells in vivo with a new nano-sized MRI contrast agent.

Unlabelled: Non-invasive in vivo tracking of T-cells by magnetic resonance imaging (MRI) can lead to a better understanding of many pathophysiological situations, including AIDS, cancer, diabetes, graft rejection. However, an efficient MRI contrast agent and a reliable technique to track non-phagocytic T-cells are needed. We report a novel superparamagnetic nano-sized iron-oxide particle, IOPC-NH2 series particles, coated with polyethylene glycol (PEG), with high transverse relaxivity (250 s(-1) mM(-1)), thus useful for MRI studies.

Paclitaxel and iron oxide loaded multifunctional nanoparticles for chemotherapy, fluorescence properties, and magnetic resonance imaging.

The multifunctional nanoparticles constructed from triphenylamine-poly(lactide-co-glycolide)-poly(ethyleneglycol)-poly(lactide-co-glycolide) (TPA-PEP) and folate-poly(2-ethyl-2oxazoline)-poly(D,L-lactide) (folate-PEOz-PLA) were developed in this study. Iron oxide nanoparticles (IOP) and paclitaxel (PTX) were coencapsulated in the nanoparticles with diameter less than 200 nm. The drug-loaded nanoparticles emit fluorescence peak at 460 nm when excited with wavelength of 350 nm.

Effects of surface modification of PLGA-PEG-PLGA nanoparticles on loperamide delivery efficiency across the blood-brain barrier.

In this study, we developed a nanoparticle system for drug delivery across the blood-brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated.

Fluorescent magnetic nanoparticles with specific targeting functions for combinded targeting, optical imaging and magnetic resonance imaging.

Superparamagnetic iron oxides nanoparticles possess specific magnetic properties to be an efficient contrast agent for magnetic resonance imaging (MRI) to enhance the detection and characterization of tissue lesions within the body. To endow specific properties to nanoparticles that can target cancer cells and prevent recognition by the reticuloendothelial system (RES), the surface of the nanoparticles was modified with folic-acid-conjugated poly(ethylene glycol) (FA-PEG). In this study, we investigated the multifunctional fluorescent magnetic nanoparticles (IOPFC) that can specifically target cancer cells and be monitored by both MRI and optical imaging.

A new nano-sized iron oxide particle with high sensitivity for cellular magnetic resonance imaging.

Purpose: In this study, we investigated the labeling efficiency and magnetic resonance imaging (MRI) signal sensitivity of a newly synthesized, nano-sized iron oxide particle (IOP) coated with polyethylene glycol (PEG), designed by Industrial Technology Research Institute (ITRI).

Procedures: Macrophages, bone-marrow-derived dendritic cells, and mesenchymal stem cells (MSCs) were isolated from rats and labeled by incubating with ITRI-IOP, along with three other iron oxide particles in different sizes and coatings as reference. These labeled cells were characterized with transmission electron microscopy (TEM), light and fluorescence microscopy, phantom MRI, and finally in vivo MRI and ex vivo magnetic resonance microscopy (MRM) of transplanted hearts in rats infused with labeled macrophages.

Polycation/DNA complexes coated with oligonucleotides for gene delivery.

Ternary nanoparticles with negatively charged surface were prepared by coating single-stranded oligonucleotides (5'-C(10)A(20)-3') on histidine-conjugated polyallylamine (PAA-HIS)/DNA complexes for gene delivery. Characterization of PAA-HIS/DNA/oligonucleotide complexes demonstrated that nanoparticles possessed the negative surface charge -27 mV and size of around 100 nm when the molar ratio of oligonucleotide/PAA-HIS exceeded 1.5.

Structural and physical characterization of tetranuclear [Mn(II)3Mn(IV)] and [Mn(II)2Mn(III)2] valence-isomer manganese complexes.

Two tetranuclear Mn complexes with an average Mn oxidation state of +2.5 have been prepared. These valence isomers have been characterized by a combination of X-ray crystallography, X-ray absorption spectroscopy, and magnetic susceptibility.

In search of elusive high-valent manganese species that evaluate mechanisms of photosynthetic water oxidation.

Significant progress in the understanding of biological water oxidation has occurred during the past 25 years. Today we have a somewhat clearer description of the structure of the Mn4Ca cluster and an idea of the appropriate oxidation states for the enzyme during catalysis. At issue is the mechanism of water oxidation.

Synthesis and characterization of a novel macrocyclic chelator with 3-hydroxy-4-pyrone chelating arms and its complexes with medicinally important metals.

A new macrocyclic chelator, 6,6',6''-(1,4,7-triazonane-1,4,7-triyl)tris(methylene)tris(5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) (H3NOKA), was synthesized from the reaction of 1 equiv of 1,4,7-triazacyclononane (TACN) and 3 equiv of kojic acid (KA) in the presence of excess formaldehyde. The reaction of H 3NOKA with metal salt forms complexes M(NOKA) (M = Ga, In, and Fe) and Cu(HNOKA). H 3NOKA and its complexes, M(NOKA) (M = Ga, In, and Fe) and Cu(HNOKA), have been characterized by IR, UV/vis, ESI-MS, and elemental analysis.

Coligand effects on the solution stability, biodistribution and metabolism of the (99m)Tc-labeled cyclic RGDfK tetramer.

In this study, we present the evaluation of two new ternary ligand (99m)Tc complexes [(99m)Tc(HYNIC tetramer)(tricine)(L)] [L=isonicotinic acid (ISONIC) and 2,5-pyridinedicarboxylic acid (PDA)] as potential radiotracers for tumor imaging. Athymic nude mice bearing MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. Solution stability data showed that [(99m)Tc(HYNIC tetramer)(tricine)(L)] (L=ISONIC and PDA) had significant decomposition (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand.

Impact of bidentate chelators on lipophilicity, stability, and biodistribution characteristics of cationic 99mTc-nitrido complexes.

This report describes synthesis and evaluation of novel cationic 99mTc-nitrido complexes, [99mTcN(L)(PNP)](+) (L = ma, ema, tma, etma and mpo; PNP = PNP5, PNP6, and L6), as potential radiotracers for heart imaging. Cationic complexes [99mTcN(L)(PNP)](+) were prepared in two steps. For example, reaction of succinic dihydrazide with 99mTcO4(-) in the presence of excess stannous chloride and PDTA resulted in the [99mTcN(PDTA)n] intermediate, which then reacted Hmpo and PNP6 at 100 degrees C for 10-15 min to give [99mTcN(mpo)(PNP6)](+) in >90% yield.

Evaluation of a (99m)Tc-labeled cyclic RGD tetramer for noninvasive imaging integrin alpha(v)beta3-positive breast cancer.

Integrin alphavbeta3 plays a critical role in tumor angiogenesis and metastasis. Radiolabeled RGD peptides that are integrin alphavbeta3-specific are very useful for noninvasive imaging of integrin expression in rapidly growing and metastatic tumors. In this study, we determined the binding affinity of E{E[c(RGDfK)]2}2 (tetramer) and its 6-hydrazinonicotinamide conjugate (HYNIC-tetramer) against the binding of 125I-echistatin to the integrin alphavbeta3-positive MDA-MB-435 breast cancer cells.

Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging.

This report describes the evaluation of three cationic (99m)Tc(I)-tricarbonyl complexes--[(99m)Tc(CO)(3)(L)](+) (L=N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (18C6-PNP))--as potential radiotracers for myocardial perfusion imaging. Biodistribution, imaging and metabolism studies were performed using Sprague-Dawley rats. It was found that bisphosphine ligands have a significant impact on the biodistribution characteristics and clearance kinetics of their cationic (99m)Tc(I)-tricarbonyl complexes.