The development of drug delivery systems (DDSs) has raised hopes for targeted
cancer therapy.
Smart polymers can be conjugated with several nanoparticles and increase their efficiency in biomedical applications. In this work, the classical molecular dynamics and well-tempered metadynamics simulations are performed to study the behavior of
black phosphorus (BPH) nanosheet functionalized with
polyethylenimine (PEI) in adsorption, diffusion, and release of
doxorubicin (DOX) anticancer
drug. Adsorption of the
drug on PEI-BPH surface is mainly due to the formation of strong pi-pi interaction between the
drug and BPH. The
drug-binding to the nanosheet is enhanced by the intermolecular hydrogen bond that formed between DOX and PEI. The energy values for the interaction of DOX with BPH and PEI are calculated to be about - 180 and - 50 kJ/mol, respectively. The obtained results indicated that the adsorption of the
drug molecules on the nanosheet destroyed the hydration layer around the BPH-PEI surface. The free energy calculation for DDS shows a global minimum in which the distances of DOX from BPH surface and PEI are about 1.0 and 0.5 nm, respectively. Furthermore, the diffusion of DDS into the membrane has a macropinocytosis pathway that is in line with experimental observations. Moreover, it is found that, unlike the isolated DOX, the
drug in complex with BPH-PEI can be easily penetrated membrane cells. The study of the pH-responsive release of the
drug shows the high solubility of the
polymer in the water environment plays the main role in swelling of DDS and the release of the DOX molecules.