Design and Development of Dual Responsive Nanocarrier Based on Tungsten Disulfide Nanosheets and Its Cytotoxic Effect on PC-3 Cells as an Efficient In Vitro Drug Delivery System for Flutamide

Abstract

In this work, flutamide‐loaded tungsten disulfide nanosheets modified thermo-responsive polymer (N-vinylcaprolactam) were prepared as a dual responsive system for targeted delivery of flutamide to tumor cells. The prepared nanocarrier was characterized using field-emission scanning electron microscopy, atomic force microscopy, Zeta potential, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermal gravimetric analyses. The behavior of flutamide sorption was investigated by non-linear isotherm models that the equilibrium data well fitted with the Langmuir model. The maximum sorption capacity of the drug as computed from the non-linear Langmuir model was 7.33 mg g^–1. Moreover, the kinetics of the sorption procedure followed by the non-linear pseudo-2nd-order kinetic model with a higher regression coefficient (R² = 0.9965). The pH and temperature-responsive nanocarrier released minimal amounts (15.75%) of the drug at a simulated physiological medium (pH 7.4; T = 37 °C). In contrast, a fast release of the drug (77.52%) was shown in a simulated cancer medium at a high temperature after 6 h (pH 5.6; T = 45 °C). Furthermore, the released amounts of drug from the nanocarrier can be regulated by adjusting the near-infrared laser irradiation. Dual responsive nanocarrier shown targeted cytotoxicity towards PC-3 cells with milder cytotoxicity towards normal cells. The nanocarrier showed two-fold higher cytotoxicity under near-infrared laser irradiation in comparison to the nanocarrier without irradiation in the PC-3 cell lines. Enhanced antitumor efficacy by photo-thermal therapy was achieved with near-infrared laser irradiation. All these data suggest that the pH and temperature dual responsive nanocarrier is a biocompatible and efficient candidate for the specific delivery of flutamide to PC-3 cells and could be utilized as a prostate cancer specific drug delivery system.