In Vitro and In Vivo Evaluations of Mesoporous Iron Particles for Iron Bioavailability.

Chronic renal failure involving hemodialysis results in blood loss during filtration. Iron deficiency and iron deficiency anemia can result. A compensatory increase in iron dosage has many side effects including discomfort. Elemental iron is a highly-pure iron source, which reduces the frequency of dosages; the solubility decreases with increased particle size or pore size. In this study, synthesized mesoporous iron particles (MIPs) were used to relieve iron deficiency anemia. Their bioavailability was measured in vitro by a Caco-2 cell model and in vivo in iron-deficient rats. In vitro bioavailability of MIPs was examined by measuring ferritin content in the Caco-2 cell model. Iron uptake of MIPs was significantly higher than commercial iron particles, which were less porous. In vivo bioavailability of MIPs was examined by measuring body weight gain and red blood cell-related parameters, compared with the bioavailability of standard drug ferrous sulfate in iron-deficient anemic rats. Finally, average hemoglobin content and hemoglobin regeneration efficiency were significantly higher in anemic rats supplemented with commercial iron particles, compared to anemic controls. In the 28-day oral toxicity test, MIPs were not significantly toxic to rat physiology or tissue histopathology. Thus, MIPs may allow effective recovery of hemoglobin in iron deficiency anemia.

ROS-induced HepG2 cell death from hyperthermia using magnetic hydroxyapatite nanoparticles.

HepG2 cell death with magnetic hyperthermia (MHT) using hydroxyapatite nanoparticles (mHAPs) and alternating magnetic fields (AMF) was investigated in vitro. The mHAPs were synthesized as thermo-seeds by co-precipitation with the addition of Fe2+. The grain size of the HAPs and iron oxide magnetic were 39.1 and 19.5 nm and were calculated by the Scherrer formula. The HepG2 cells were cultured with mHAPs and exposed to an AMF for 30 min yielding maximum temperatures of 43 ± 0.5 °C. After heating, the cell viability was reduced by 50% relative to controls, lactate dehydrogenase (LDH) concentrations measured in media were three-fold greater than those measured in all control groups. Readouts of toxicity by live/dead staining were consistent with cell viability and LDH assay results. Measured reactive oxygen species (ROS) in cells exposed to MHT were two-fold greater than in control groups. Results of cDNA microarray and Western blotting revealed tantalizing evidence of ATM and GADD45 downregulation with possible MKK3/MKK6 and ATF-2 of p38 MAPK inhibition upon exposure to mHAPs and AMF combinations. These results suggest that the combination of mHAPs and AMF can increase intracellular concentrations of ROS to cause DNA damage, which leads to cell death that complement heat stress related biological effects.

Laminin-Alginate Beads as Preadipocyte Carriers to Enhance Adipogenesis In Vitro and In Vivo.

The use of autologous fat grafting in breast reconstruction still requires optimization. Fat survival and calcification are the main issues that affect the outcomes of the procedure. In this study, a cell-based therapy utilizing laminin-alginate beads (LABs) as carriers was proposed to promote cell survival and adipogenesis by providing short-term physical support and facilitate nutrient diffusion of the implants. Laminin-modified alginate beads were fabricated by immobilizing laminin onto ring-opened alginate, used to encapsulate 3T3-L1 preadipocytes, and evaluated in vitro and in vivo. LABs as preadipocyte carriers showed better biocompatibility and stability than unmodified alginate beads. Preadipocytes in LABs had higher survival rate and enhanced adipogenesis than those in unmodified alginate beads. In vivo studies showed that LABs gradually degraded and the sites were replaced by newly formed fat tissues, and new blood vessels were also observed. 7T-MRI study mimicking clinical fat grafting showed that LABs carrying adipose stem cells improved the results of conventional fat grafts. Therefore, we believe that LABs represent promising cell carriers and can be potentially used for the reconstruction of breasts or other soft tissues in the future.