Dual-responsive drug carrier based on zeolitic imidazolate framework-8 incorporated into gold nanoparticles/chitosan/copper sulfide for controlled drug delivery

Abstract

Currently, two major obstacles in effective treatment of breast cancer are development of resistance to chemotherapeutic drugs by cancer cells and the off-target cytotoxicity of these drugs. The main aim of this study was to synthesize a dual responsive nanocarrier by incorporating the zeolitic-imidazolate framework-8 into the gold nanoparticles/chitosan/copper sulfide for controlled release of doxorubicin. The prepared nanocarrier was characterized using various techniques, including Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, and zeta potentials. The optimum experimental conditions, including adsorbent dosage (0.01–0.03 g), pH of solutions (5–9), contact time (5–15 min), and temperature (25–45 °C) at three levels were studied using the central composite design based on the response surface methodology. Our results indicated highest response (99 %) with 0.03 g of nanocarrier, at pH of 5, time of 10 min, and temperature of 35 °C. The obtained data were further studied with seven isotherm models. Based on the lower error sum of square values (0.059–0.514) and higher correlation coefficient values (0.9857–0.9972), Langmuir and Sips isotherm models were observed to be the best fitted. The in-vitro drug release study indicated 37.97 % of the drug being released in the simulated environment with physiological conditions, while 71.29 % of the drug was released in the simulated cancer cells condition at higher temperature. This data confirms the pH and temperature sensitivity of the nanocarrier. Enhanced drug release from the nanocarrier indicated low cell viability in the breast cancer cell line (MCF-7) under near-infrared laser irradiation. The IC50 values of nanocarrier and pure drug in MCF-7 cells were 243.95 and 4.442 μg L−1, respectively. Based on these data, we are concluding that our dual responsive nanocarrier has the potential to overcome the problems development of resistance of cancer cells and toxicity associated with current treatment of breast cancer.