Gd-Doped Superparamagnetic Magnetite Nanoparticles for Potential Cancer Theranostics

Nanotechnology has facilitated the applications of a class of nanomaterials called superparamagnetic iron oxide nanoparticles (SPIONs) in cancer theranostics. This is a new discipline in biomedicine that combines therapy and diagnosis in one platform. The multifunctional SPIONs, which are capable of detecting, visualizing, and destroying the neoplastic cells with fewer side effects than the conventional therapies, are reviewed in this chapter for theranostic applications. The chapter summarizes the design parameters such as size, shape, coating, and target ligand functionalization of SPIONs, which enhance their ability to diagnose and treat cancer. The review discusses the methods of synthesizing SPIONs, their structural, morphological, and magnetic properties that are important for theranostics. The applications of SPIONs for drug delivery, magnetic resonance imaging, and magnetic hyperthermia therapy (MHT) are included. The results of our recent MHT study on Gd-doped SPION as a possible theranostic agent are highlighted. We have also discussed the challenges and outlook on the future research for theranostics in clinical settings

Determination of Magnetic Exchange Stiffness and Surface Anisotropy Constants in Epitaxial Ni_ {1-x} Co_ {x}(001) Films

Magnetic characteristics of epitaxial Ni1-xCox(001) (x=0, 0.16, and 0.50) films with nominal 200 nm thickness on Cu(001)/Si(100) substrates have been investigated by magnetization and ferromagnetic resonance measurements in order to better clarify the rationale for the large variation in the magnetic exchange stiffness constant A, previously determined from different measurements. The exchange constant as well as the saturation magnetization, effective demagnetizing field, fourth-order magnetocrystalline, and second-order perpendicular uniaxial magnetic anisotropy fields has been determined. The analyses of low-temperature saturation magnetization data on these films yield A values that increase from 0.82×10-6erg/cm for a pure Ni film to 2.27×10-6erg/cm for the Ni0.50Co0.50 film. Furthermore, spin-wave resonance volume modes observed in x=0 and 0.16 films indicate that the surface plays a role in the exchange stiffness constant determination as the surface anisotropy constants are found to be approximately 1 and 4 erg/cm2, respectively. The latter value is substantially larger than that for any other system reported so far

A method for measuring the Neel relaxation time in a frozen ferrofluid

We report a novel method of determining the average Neel relaxation time and its temperature dependence by calculating derivatives of the measured time dependence of temperature for a frozen ferrofluid exposed to an alternating magnetic field. The ferrofluid, composed of dextran-coated Fe3O4 nanoparticles (diameter 13.7 nm +/- 4.7 nm), was synthesized via wet chemical precipitation and characterized by x-ray diffraction and transmission electron microscopy. An alternating magnetic field of constant amplitude (H0 = 20 kA/m) driven at frequencies of 171 kHz, 232 kHz and 343 kHz was used to determine the temperature dependent magnetic energy absorption rate in the temperature range from 160 K to 210 K. We found that the specific absorption rate of the ferrofluid decreased monotonically with temperature over this range at the given frequencies. From these measured data, we determined the temperature dependence of the Neel relaxation time and estimate a room-temperature magnetocrystalline anisotropy constant of 40 kJ/m3, in agreement with previously published results

Clinical pharmacology of exogenously administered alkaline phosphatase

Purpose: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). Methods: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg-124 h-1) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. Results: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. Conclusions: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis

Paneth cells as a site of origin for intestinal inflammation.

The recognition of autophagy related 16-like 1 (ATG16L1) as a genetic risk factor has exposed the critical role of autophagy in Crohn's disease. Homozygosity for the highly prevalent ATG16L1 risk allele, or murine hypomorphic (HM) activity, causes Paneth cell dysfunction. As Atg16l1(HM) mice do not develop spontaneous intestinal inflammation, the mechanism(s) by which ATG16L1 contributes to disease remains obscure. Deletion of the unfolded protein response (UPR) transcription factor X-box binding protein-1 (Xbp1) in intestinal epithelial cells, the human orthologue of which harbours rare inflammatory bowel disease risk variants, results in endoplasmic reticulum (ER) stress, Paneth cell impairment and spontaneous enteritis. Unresolved ER stress is a common feature of inflammatory bowel disease epithelium, and several genetic risk factors of Crohn's disease affect Paneth cells. Here we show that impairment in either UPR (Xbp1(ΔIEC)) or autophagy function (Atg16l1(ΔIEC) or Atg7(ΔIEC)) in intestinal epithelial cells results in each other's compensatory engagement, and severe spontaneous Crohn's-disease-like transmural ileitis if both mechanisms are compromised. Xbp1(ΔIEC) mice show autophagosome formation in hypomorphic Paneth cells, which is linked to ER stress via protein kinase RNA-like endoplasmic reticulum kinase (PERK), elongation initiation factor 2α (eIF2α) and activating transcription factor 4 (ATF4). Ileitis is dependent on commensal microbiota and derives from increased intestinal epithelial cell death, inositol requiring enzyme 1α (IRE1α)-regulated NF-κB activation and tumour-necrosis factor signalling, which are synergistically increased when autophagy is deficient. ATG16L1 restrains IRE1α activity, and augmentation of autophagy in intestinal epithelial cells ameliorates ER stress-induced intestinal inflammation and eases NF-κB overactivation and intestinal epithelial cell death. ER stress, autophagy induction and spontaneous ileitis emerge from Paneth-cell-specific deletion of Xbp1. Genetically and environmentally controlled UPR function within Paneth cells may therefore set the threshold for the development of intestinal inflammation upon hypomorphic ATG16L1 function and implicate ileal Crohn's disease as a specific disorder of Paneth cells