Cancer is one of the most common diseases nowadays and derives from the uncontrollable growth of a single cell. Magnetic nanoparticles (NpMag) offer various possibilities for use in the biomedical area, including drug delivery mediated by magnetic fields. In the current study, we evaluated the in vitro effects of iron-oxide magnetic nanoparticles conjugated with the antitumor drug doxorubicin (Dox) on human breast cancer cells. Our results revealed that magnetic nanoparticles with Dox (NpMag+Dox) induce cellular redox imbalance in MCF-7 cells. We also demonstrate that iron-oxide nanoparticles functionalized with Dox induce oxidative stress evidenced by DNA damage, lipid peroxidation, cell membrane disruption, and loss of mitochondria potential. As a result, NpMag+Dox drives MCF-7 cells to stop the cell cycle and decrease cell migration. The association of NpMg+Dox induced a better delivery of Dox to MCF cells, mainly in the presence of a magnetic field, increasing the death of MCF cells which might reduce the toxicity for healthy cells providing a better efficacy for the treatment. Thus, iron-oxide nanoparticles and doxorubicin conjugated may be candidate for anticancer therapy.

In this study, we show the synthesis of novel hybrid organic–inorganic aerogel materials with one-dimensionally aligned pores and demonstrate their use as sustained and prolonged release systems for a hydrophobic drug. The materials are synthesized by trapping mesoporous silica nanoparticles within a hyperbranched polymer network made from poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA). The synthetic method involves dispersing mesoporous silica nanoparticles in a polymer solution, then freeze-drying the solution, and finally subjecting the resulting materials to high temperature to activate a solid-state condensation reaction between PVA and PAA. Before trapping the mesoporous silica nanoparticles within the hyperbranched polymeric network, their pores are decorated with hydrophobic groups so that they can serve as good host materials for hydrophobic drugs. The potential application of the hybrid aerogels as drug carriers is demonstrated using the hydrophobic, anti-inflammatory agent dexamethasone (DEX) as a model drug. Due to their hydrophobic pores, the hybrid aerogels show excellent drug loading capacity for DEX, with an encapsulation efficiency higher than 75%. Furthermore, the release pattern of the payloads of DEX encapsulated in the aerogels is highly tailorable (i.e., it can be made faster or slower, as needed) simply by varying the PVA-to-PAA weight ratio in the precursors, and thus the 3-dimensional (3-D) structures of the cross-linked polymers in them. The materials also show sustained drug release, for over 50 days or more. In addition, the aerogels are biocompatible, as demonstrated with Vero cells, and greatly promote the cell proliferation of L929 fibroblasts. Also, the nanoparticles functionalized with quaternary groups and dispersed within the aerogels display bactericidal activity against E. coli, S. aureus, B. subtilis, and P. aeruginosa. These new hybrid aerogels can, thus, be highly appealing biomaterials for sustained and prolonged drug release, such as wound dressing systems.

Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as hyperphosphatemia, hyperkalemia, and hypercholesterolemia. Occasionally, these drugs can irritate the gastrointestinal lining and cause life-threatening intestinal necrosis. Currently, the pathophysiology of drug crystal-induced intestinal necrosis is not well understood. We hypothesized that crystals of ion-exchange resins like sevelamer, polystyrene sulfonate, and cholestyramine can trigger the formation of neutrophil and monocyte extracellular traps by contributing to intestinal barrier dysfunction. Light and fluorescence microscopy of the colonic resection specimen from a patient with chronic kidney disease revealed severe intestinal necrosis, ulceration, sevelamer crystals, and inflammation upon oral intake of sevelamer, as well as the formation of neutrophil extracellular traps in proximity to small sevelamer crystals. Indeed, drug crystals reduced metabolic activity and induced barrier dysfunction and cell death in human intestinal epithelial cells in vitro. In addition, drug crystals triggered the release of neutrophil and monocyte extracellular traps. Taken together, these data raise the possibility that besides other factors including chronic kidney disease, diabetes mellitus, and hypertension, drug crystals may further amplify a pre-existing barrier dysfunction and necroinflammation in a crescendo of local intestinal necrosis and systemic inflammation/infection, as occasionally observed in patients on ion-exchange resin therapy.

Leishmaniasis is a neglected tropical disease caused by Leishmania species. Available therapeutic options have several limitations. The drive to develop new, more potent, and selective antileishmanial agents is thus a major goal. Herein we report the synthesis and the biological activity evaluation against promastigote and amastigote forms of Leishmania amazonensis of nine 4,8-dimethoxynaphthalenyl chalcones. Compound ((E)-1-(4,8-dimethoxynaphthalen-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one), 4f, was the most promising with an IC₅₀ = 3.3 ± 0.34 μM (promastigotes), a low cytotoxicity profile (CC₅₀ = 372.9 ± 0.04 μM), and a high selectivity index (SI = 112.6). Furthermore, 4f induced several morphological and ultrastructural changes in the free promastigote forms, loss of plasma membrane integrity, and increased reactive oxygen species (ROS). An in silico analysis of drug-likeness and ADME parameters suggested high oral bioavailability and intestinal absorption. Compound 4f reduced the number of infected macrophages and the number of amastigotes per macrophage, with an IC₅₀ value of 18.5 ± 1.19 μM. Molecular docking studies with targets, ARG and TR, showed that compound 4f had more hydrogen bond interactions with the ARG enzyme, indicating a more stable protein-ligand binding. These results suggest that 4,8-dimethoxynaphthalenyl chalcones are worthy of further study as potential antileishmanial drugs.

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the plasma effect. Taken together, neutrophils cleared hemozoin crystals from the extracellular space via endocytosis into phagosomes and vesicles without inducing the release of neutrophil extracellular traps. However, human plasma components such as fibrinogen limited hemozoin clearance, whereas the presence of platelets augmented this process. These factors may influence the pro-inflammatory potential of hemozoin crystals in malaria.

American tegumentary leishmaniasis, a zoonotic disease caused by the Leishmania genus, poses significant challenges in treatment, including administration difficulty, low efficacy, and parasite resistance. Novel compounds or associations offer alternative therapies, and natural products such as oregano essential oil (OEO), extracted from Origanum vulgare, have been extensively researched due to biological effects, including antibacterial, antifungal, and antiparasitic properties. Silver nanoparticles (AgNp), a nanomaterial with compelling antimicrobial and antiparasitic activity, have been shown to exhibit potent leishmanicidal properties. We evaluated the in vitro effect of OEO and AgNp-Bio association on L. amazonensis and the death mechanisms of the parasite involved. Our results demonstrated a synergistic antileishmanial effect of OEO + AgNp on promastigote forms and L. amazonensis-infected macrophages, which induced morphological and ultrastructural changes in promastigotes. Subsequently, we investigated the mechanisms underlying parasite death and showed an increase in NO, ROS, mitochondrial depolarization, accumulation of lipid-storage bodies, autophagic vacuoles, phosphatidylserine exposure, and damage to the plasma membrane. Moreover, the association resulted in a reduction in the percentage of infected cells and the number of amastigotes per macrophage. In conclusion, our findings establish that OEO + AgNp elicits a late apoptosis-like mechanism to combat promastigote forms and promotes ROS and NO production in infected macrophages to target intracellular amastigote forms.