The use of an appropriate delivery system capable of protecting, translocating, and selectively releasing therapeutic moieties to desired sites can promote the efficacy of an active compound. In this work, we have developed a nanoformulation which preserves its magnetization to load a model anticancerous drug and to explore the controlled release of the drug in a cancerous environment. For the preparation of the nanoformulation, self-assembled magnetic nanospheres (MNS) made of superparamagnetic iron oxide nanoparticles were grafted with a monolayer of (3-aminopropyl)triethoxysilane (APTES). A direct functionalization strategy was used to avoid the loss of the MNS magnetization. The successful preparation of the nanoformulation was validated by structural, microstructural, and magnetic investigations. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to establish the presence of APTES on the MNS surface. The amine content quantified by a ninhydrin assay revealed the monolayer coverage of APTES over MNS. The monolayer coverage of APTES reduced only negligibly the saturation magnetization from 77 emu/g (for MNS) to 74 emu/g (for MNS-APTES). Detailed investigations of the thermoremanent magnetization were carried out to assess the superparamagnetism in the MNS. To make the nanoformulation pH-responsive, the anticancerous drug Nintedanib (NTD) was conjugated with MNS-APTES through the acid liable imine bond. At pH 5.5, which mimics a cancerous environment, a controlled release of 85% in 48 h was observed. On the other hand, prolonged release of NTD was found at physiological conditions (i.e., pH 7.4). In vitro cytotoxicity study showed dose-dependent activity of MNS-APTES-NTD for human lung cancer cells L-132. About 75% reduction in cellular viability for a 100 μg/mL concentration of nanoformulation was observed. The nanoformulation designed using MNS and monolayer coverage of APTES has potential in cancer therapy as well as in other nanobiological applications.

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Over the centuries, cancer has been considered one of the significant health threats. It holds the position in the list of deadliest diseases over the globe. In women, breast cancer is the most common among many cancers and is the second most common cancer all over the world, while lung cancer is the first. Cyclin-dependent kinase 8 (CDK8) has been identified as a critical oncogenic driver that is found in breast cancer and associated with tumor progression. Flavonoids were virtually screened against CDK8 using molecular docking, drug-likeness, ADMET prediction, and a molecular dynamics (MD) simulation approach to determine the potential flavonoid structure against CDK8. The results indicated that ZINC000005854718 showed the highest negative binding affinity of −10.7 kcal/mol with the targeted protein and passed all the drug-likeness parameters. Performed molecular dynamics simulation showed that docked complex systems have good conformational stability over 100 ns in different temperatures (298, 300, 305, 310, and 320 K). The comparison between calculated binding free energy via MM/PB(GB)SA methods and binding affinity calculated via molecular docking suggested tight binding of ZINC000005854718 with targeted protein. The results concluded that ZINC000005854718 has drug-like properties with tight and stable binding with the targeted protein.

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