Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum.

Targeted delivery of nanoparticles to cells or tissues of interest is arguably the "holy grail" of nanomedicine. Using primary human macrophages and ovarian cancer cells, we evaluated the biocompatibility and specific targeting of folic acid (FA)-conjugated iron oxide nanoparticles with organic [poly(ethylene glycol), PEG] or inorganic (SiO2) intermediate surface coatings. Reduction of folate receptor-α expression using specific siRNA resulted in a significant decrease in cellular uptake of the SiO2-coated nanoparticles, but did not affect uptake of PEG-coated nanoparticles. Notably, specific (i.e. FA-dependent) uptake was observed only in the presence of serum proteins. The strategy presented here for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable targeting of nanoparticles for therapeutic and imaging applications. From the clinical editor: In this study the receptor specific uptake of folic acid-functionalized iron oxide nanoparticles was determined in ovarian cancer cells. It was found that the presence of serum proteins is an absolute requirement for the uptake of these nanoparticles. The described strategy for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable a better targeting of nanoparticles for additional therapeutic and imaging applications.

Gender medicine teaching increases medical students' gender awareness: results of a quantitative survey.

Background: Knowledge about gender implications of health is insufficiently integrated into university teaching in Germany. Gender awareness represents a key competence to integrate this knowledge into the medical practice. This study is the first survey of the gender awareness of medical students in a cross-sectional design in Germany. Methods: From April to July 2021, a quantitative cross-sectional survey in an online format using the "Nijmegen Gender Awareness in Medicine Scale" (2008) was conducted at four German universities (Charité Berlin, Friedrich-Schiller-University Jena, Ludwig-Maximilians-University Munich, and the University of Cologne) with a varied implementation of teaching gender medicine. Students indicated their agreement or disagreement with assumptions and knowledge about the influence of gender in everyday medical practice (gender sensitivity), as well as gender role stereotypes towards patients and physicians (gender role ideology). Results: The 750 included participants showed relatively high gender sensitivity and low gender role stereotyping towards patients and physicians. The curricular implementation of gender medicine in the universities showed a significant influence on the students' gender sensitivity, as well as on their gender role stereotyping towards patients. Students who reported having taken classes in gender medicine or stated a definite interest in doing so showed significantly higher levels of gender sensitivity. Cis-males showed significantly lower gender sensitivity and significantly higher gender role stereotyping. Conclusion: Implementation of gender medicine in the medical curriculum, attending courses on gender education as well as one's gender and interest have a significant impact on medical students' gender competencies. These results support the need for structural integration of gender medicine in medical education and gender trainings at medical schools in Germany.

Hollow silica capsules for amphiphilic transport and sustained delivery of antibiotic and anticancer drugs.

Hollow mesoporous silica capsules (HMSC) are potential drug transport vehicles due to their biocompatibility, high loading capacity and sufficient stability in biological milieu. Herein, we report the synthesis of ellipsoid-shaped HMSC (aspect ratio ∼2) performed using hematite particles as solid templates that were coated with a conformal silica shell through cross-condensation reactions. For obtaining hollow silica capsules, the iron oxide core was removed by acidic leaching. Gas sorption studies on HMSC revealed mesoscopic pores (main pore width ∼38 Å) and a high surface area of 308.8 m2 g-1. Cell uptake of dye-labeled HMSC was confirmed by incubating them with human cervical cancer (HeLa) cells and analyzing the internalization through confocal microscopy. The amphiphilic nature of HMSC for drug delivery applications was tested by loading antibiotic (ciprofloxacin) and anticancer (curcumin) compounds as model drugs for hydrophilic and hydrophobic therapeutics, respectively. The versatility of HMSC in transporting hydrophilic as well as hydrophobic drugs and a pH dependent drug release over several days under physiological conditions was demonstrated in both cases by UV-vis spectroscopy. Ciprofloxacin-loaded HMSC were additionally evaluated towards Gram negative (E. coli) bacteria and demonstrated their efficacy even at low concentrations (10 µg ml-1) in inhibiting complete bacterial growth over 18 hours.

Enhanced in vitro and in vivo cellular imaging with green tea coated water-soluble iron oxide nanocrystals.

Fully green and facile redox chemistry involving reduction of colloidal iron hydroxide (Fe(OH)3) through green tea (GT) polyphenols produced water-soluble Fe3O4 nanocrystals coated with GT extracts namely epigallocatechin gallate (EGCG) and epicatechin (EC). Electron donating polyphenols stoichiometrically reduced Fe(3+) ions into Fe(2+) ions resulting in the formation of magnetite (Fe3O4) nanoparticles and corresponding oxidized products (semiquinones and quinones) that simultaneously served as efficient surface chelators for the Fe3O4 nanoparticles making them dispersible and stable in water, PBS, and cell culture medium for extended time periods. As-formed iron oxide nanoparticles (2.5-6 nm) displayed high crystallinity and saturation magnetization as well as high relaxivity ratios manifested in strong contrast enhancement observed in T2-weighted images. Potential of green tea-coated superparamagnetic iron oxide nanocrystals (SPIONs) as superior negative contrast agents was confirmed by in vitro and in vivo experiments. Primary human macrophages (J774A.1) and colon cancer cells (CT26) were chosen to assess cytotoxicity and cellular uptake of GT-, EGCGq-, and ECq-coated Fe3O4 nanoparticles, which showed high uptake efficiencies by J774A.1 and CT26 cells without any additional transfection agent. Furthermore, the in vivo accumulation characteristics of GT-coated Fe3O4 nanoparticles were similar to those observed in clinical studies of SPIONs with comparable accumulation in epidermoid cancer-xenograft bearing mice. Given their promising transport and uptake characteristics and new surface chemistry, GT-SPIONs conjugates can be applied for multimodal imaging and therapeutic applications by anchoring further functionalities.

Bioconjugated iron oxide nanocubes: synthesis, functionalization, and vectorization.

A facile bottom-up approach for the synthesis of inorganic/organic bioconjugated nanoprobes based on iron oxide nanocubes as the core with a nanometric silica shell is demonstrated. Surface coating and functionalization protocols developed in this work offered good control over the shell thickness (8-40 nm) and enabled biovectorization of SiO2@Fe3O4 core-shell structures by covalent attachment of folic acid (FA) as a targeting unit for cellular uptake. The successful immobilization of folic acid was investigated both quantitatively (TGA, EA, XPS) and qualitatively (AT-IR, UV-vis, ζ-potential). Additionally, the magnetic behavior of the nanocomposites was monitored after each functionalization step. Cell viability studies confirmed low cytotoxicity of FA@SiO2@Fe3O4 conjugates, which makes them promising nanoprobes for targeted internalization by cells and their imaging.

SiO2@Fe2O3 core-shell nanoparticles for covalent immobilization and release of sparfloxacin drug.

Silica-coated Fe(2)O(3) nanoparticles were synthesized as carriers for the covalent immobilization and release of antimicrobial drug sparfloxacin (SPFX). SPFX-loaded nanoparticles exhibited time-dependent drug release, with no measurable in vitro cytotoxicity, making the drug@nanoparticle conjugates potentially relevant for nanomedicine applications.