Exploring anticancer potential of nintedanib conjugated magnetic nanoparticles: In-vitro and in-silico studies

Magnetic nanoparticles (MNPs) are studied widely as nanocarriers in targeted drug delivery systems (TDDs). Anticancer drugs conjugated MNPs were designed to release a drug at the targeted site by pH stimuli and reduce exposure to healthy cells. In the present study, MNPs are prepared by the co-precipitation method, conjugated with the anticancer drug Nintedanib (NIN) via acid-labile imine bond, and optimized for conjugation efficiency and drug content. FTIR, EDX, XRD, FESEM, VSM, BET, and DLS were used for characterization of structural, physicochemical, and morphological properties of the MNPs. The characterization studies of MNPs revealed optimally sized, spherical particles that preserved their magnetization and supported the formation of imine bonds. To analyze the drug released in an acidic environment, NIN release behavior from conjugated MNPs was examined at pH 5.5 and pH 7.4. The IC50 values and toxicity of drug-conjugated MNPs against healthy HEK-293 cells and A549 cancer cells were evaluated using dose-dependent cytotoxicity tests. Further, Hemolysis and brine shrimp assay were conducted to observe biocompatibility and toxicity studies. In-silico analysis, such as molecular dynamics simulation, docking, drug-likeness, and ADMET analysis, resulted in stable hydrogen bonding interactions at the vascular endothelial growth factors (VEGFR) kinase domain. Thus, NIN-conjugated MNPs were found to exhibit an efficient nanocarrier for cancer targeting.