Molecular insight into the role of benzotriazole nanocapsule to deliver anticancer drug in smart drug delivery system

Abstract

The use of nanomaterials as drug delivery systems is an area of interest for various anticancer drugs, aiming to minimize their side effects while ensuring they reach the target site effectively. In the current study, Benzotriazole capsule as drug delivery system for cyclophosphamide (CP) and gemcitabine (GB) drugs adsorption is explored. Various electronic and structural parameters shows that both drugs have good interaction with nanocapsule and can be carried to the target site easily. The calculated binding energies of drug@Capsule complexes are in the range of -43.34 and - 56.64 kcal/mol, which shows stronger interaction of drug molecules with nanocapsule. The noncovalent interactions between CP, GB and capsule are confirmed through QTAIM and NCI analyses. NBO analysis is used to understand the shifting of electron density, which shifts from drug to surface. FMO analysis is performed to estimate the perturbations in the electronic parameters upon complexation, which reveals reduction in the E_H-L gap. Moreover, pH effect and dipole moment analysis are performed to get insight into the drug release mechanism. Dipole moment values indicate that nanocapsule can effectively release CP drug on a target site. The findings suggest that benzotriazole capsule surface is highly selective toward CP and GB.

Keywords: Anticancer agents; Benzotriazole capsule; Density-functional theory; Drug delivery; Gemcitabine; Sensing.

Fig. 1

Optimized geometries and simple images of studied anticancer drugs.

Fig. 2

Stable structure of capsule at the M06-2X/6-31G(d, p) level of theory (blue, red, white and grey represent nitrogen, oxygen, hydrogen, and carbon, respectively).

Fig. 3

The most stable geometries of drugs@Capsule complexes at the M06-2X/6-31G(d, p) level of theory.

Fig. 4

NCI 3D isosurfaces and 2D-RDG plots of stable CP@Capsule and GB@Capsule complexes at isovalue of 0.004 a.u. (red, green and blue color indicate steric repulsions, weak van der Waal’s forces and blue hydrogen bonding.

Fig. 5

QTAIM analysis of studied drugs@Capsule complexes and orange-colored dots indicate the BCPs, whereas yellow lines between drug and capsule shows bond paths.

Fig. 6

EDD plots of drugs@capsule with Blue isosurfaces represent electron density accumulation, and red isosurfaces shows electron density depletion (Isovalue = 0.004 a.u.).

Fig. 7

Optimized structures of drug-capsule complexes after protonation at M06-2X/6-31G(d, p) level of theory.

Fig. 8

The interaction diagram of Cyclophosphamide with Human Deoxyribonucleic acid (hDNA) in terms of (A) Aromatic, (B) H-bonds, (C) 3D structure of interpolated charges, and (D) 2D diagram.

Fig. 9

The visual representation of interactions between Gemcitabine and Ribonucleoside-diphosphate reductase M2 (RRM2) in terms of (A) aromatic, (B) H-bonds, (C) 3D structure of interpolated charges, (D) 2D diagram of interactions.

Fig. 10

The visual representation of interactions of Gemcitabine with Mutated KRAS (mKRAS) in terms of (A) Aromatic, (B) H-bonds, (C) 3D structure of interpolated charges, and (D) 2D diagram of interactions.