Predictions of Drug–Protein Interactions and Study of Magnetically Assisted Release Dynamics of 5-Fluorouracil from Soya Protein-Coated Iron Oxide Core–Shell Nanoparticles

Abstract

In silico studies were performed using 5-fluorouracil (5-FU) to explore the efficacy of template docking and facilitate designing of drug nanocarrier systems. The binding of human uridine phosphorylase (huPP1) with 5-FU was found to show the following interactions: (1) hydrogen bonds were alleviated by a network of GLN217 and ARG219, (2) hydrophobic interactions were shown by PHE213, THR141, LEU272, and ILE281 (3) positive electrostatic interactions were shown by PHE213, THR141, LEU272, SER142, GLU248, and GLY143. As an experimental supplementation and validation to the adopted computational approach, 5- FU-loaded soya protein-coated iron oxide (SPCIO) core–shell nanoparticles were prepared following microemulsion and co-precipitation techniques and subsequently characterized by FTIR, particle size and zeta potential studies, TEM, XRD, and DSC techniques. Whereas the FTIR spectra confirm the presence of the soya protein and drug 5-FU in the nanoparticles, the zeta potential was found to be suppressed due to the loading of 5-FU. The XRD study confirmed the crystalline nature of the drug-loaded nanoparticles. TEM analysis suggested that the nanoparticles have sizes up to 200 nm and the morphology and size remain almost the same even after loading of the drug 5-FU onto nanoparticles. The soya protein-coated iron oxide nanoparticles demonstrated zero cytotoxicity against fibroblast cells. The controlled release of 5-FU was studied in vitro, and the effects of pH, chemical composition of nanoparticles, extent of drug loading, and simulated biofluids on the controlled release of 5-FU were studied. The swelling of nanoparticles and release of 5-FU were found to increase with increasing strength of the externally applied magnetic field.

Magnetic-field-triggered Remote Drug Release and Analysis of Mechanism

“…Although some achievements have made, there are still obstacles to overcome such as the controllable drug release behavior in the physical medium and the adsorption between the protein and the drug. (16) Most researchers consider that the drug release mechanism triggered by an LF-AMF is based on the permeability change of the carrier shell caused by the magnetic thermal and magnetic oscillation effects, which subsequently promote drug release. (17) In most cases, the role of the magnetic thermal effect is dominant relative to that of the magnetic oscillation effect of MNPs in LF-AMFs.…”

Modulating the Delivery of 5-Fluorouracil to Human Colon Cancer Cells Using Multifunctional Arginine-Coated Manganese Oxide Nanocuboids with MRI Properties

“…5-Fluorouracil (5-FU) is a clinically approved anticancer drug for the treatment of solid tumors including colorectal, gastric, skin, and breast cancers. , It is used either alone or in combination with other chemotherapeutic agents. 5-FU is widely used as a first-line chemotherapeutic agent for the treatment of metastatic colon cancer along with oxaliplatin and leucovorin .…”