Magnetic Nanoplatform With Novel Potential for the Treatment of Bone Pathologies: Drug Loading and Biocompatibility on Blood and Bone Cells.

Magnetic iron oxide nanoparticles (MNPs) coated with citric acid (MG@CA) are proposed as raw materials for the treatment of bone diseases. Citric acid (CA) was selected as coating due to its role in the stabilization of apatite nanocrystals and as a signaling agent for osteoblast activation. Raloxifene (Ral), curcumine (Cur) and methylene blue (MB) were employed as model drugs as therapeutic agents for bone diseases. Characterization of raw and drug loaded nanosystems was conducted in order to elucidate the mechanisms governing interactions between therapeutics and the magnetic platform. Biocompatibility studies were performed on red blood cells (RBCs) from peripheral human blood. Cytotoxicity was evaluated on endothelial cells (ECs); and viability was studied for bone cells exposed at concentrations of 1, 10 and 100 [Formula: see text]/mL of the magnetic nano-platform. MG@CA exhibited proper physicochemical properties for the applications intended within this work. It presented satisfactory biocompatibility on peripheral red blood cells. Only doses of 100 [Formula: see text]/mL induced a decrease in metabolic activity of ECs and MC3T3-E1 cells. Drug adsorption efficiency was estimated as 62.0, 15.0 and 54.0 % for Ral, Cur and MB and drug loading capability of 12.0, 20.0 and 13.6%, respectively.

Doxorubicin delivery by magnetic nanotheranostics enhances the cell death in chemoresistant colorectal cancer-derived cells.

Colorectal cancer (CRC) is a major cause of cancer death with a high probability of treatment failure. Doxorubicin (DOXO) is an efficient antitumor drug; however, most CRC cells show resistance to its effects. Magnetic nanoparticles (MNPs) are potential cancer management tools that can serve as diagnostic agents and also can optimize and personalize treatments. This work aims to evaluate the aptitude of magnetic nanotheranostics composed of magnetite (Fe3O4) nanoparticles coated with folic acid intended to the sustained release of DOXO. The administration of DOXO by means of these MNPs resulted in the enhancement of cell death respect to the free drug administration. Chromatin compaction and cytoplasmic protrusions were observed. Mitochondrial transmembrane potential disruption and increased PARP protein cleavage confirmed apoptosis. The nanosystem was also tested as a vectoring tool by exposing it to the stimuli of a static magnetic field in vitro. CRC-related magnetic nanotechnology still remains in pre-clinical trials. In this context, this contribution expands the knowledge of the behavior of MNPs in contact with in vitro models and proposes the nanodevices studied here as potential theranostic agents for the monitoring of the progress of CRC and the evolution of its treatment.

Folic acid magnetic nanotheranostics for delivering doxorubicin: Toxicological and biocompatibility studies on Zebrafish embryo and larvae.

Doxorubicin (DOXO) is a chemotherapeutic agent widely used for the treatment of solid tumors and hematologic malignancies in both adults and children. However, DOXO causes short- and long-term cardiotoxicity and others undesirable side effects, such as nephrotoxicity and neurotoxicity. Magnetic nanoparticles (MNPs) allow the delivery of drugs specifically to target place, employing an external magnet. Moreover, they may act as contrast agents in MRI providing information on the diagnostic of diverse pathologies. In this way, two functions may be combined in a unique nanosystem known as theranostic. Also, the MNPs can be modified with folic acid (MNPs@FA) to increase the uptake by cancer cells that overexpress the FA receptors. In previous works, our collaborators obtained and characterized MNPs, MNPs@FA, and MNPs@FA@DOXO. It is essential to study the biosafety of nanotheranostic, and there is no published study of Fe3O4 nanoparticles developmental toxicity. Because of that, this work aimed to study the in vivo toxicity and biocompatibility of DOXO, MNPs@FA, and MNPs@FA@DOXO using zebrafish embryo and larvae as an animal model. Viability, developmental toxicity, changes in spontaneous movement (neurotoxicity), changes in cardiac rhythm (cardiotoxicity), and efficiency of DOXO-uptake were studied. While the 48-h treatment with 50 µg/mL of DOXO resulted in a 30% larvae death and the development of significant morphological abnormalities, the treatment with MNPs@FA@DOXO and MNPs@FA did not reduce the viability and did not cause developmental abnormalities. Besides, the MNPs@FA@DOXO reduced the cardiotoxicity and promoted a more rapid and significant uptake of DOXO by zebrafish larvae.