Chitosan/copper sulfide nanoparticles conjugated with Paclitaxel for combinational therapy of breast cancer

Abstract

Introduction: Photothermal therapy (PTT) is a laser-based, targeted technique for burning tumor cells that is induced by light-heat conversion in cancer cells until the cells die. Its combination with chemotherapy can be an effective strategy for resistant cancer types.Objectives: In this study, we combined chitosan coated copper sulfide nanoparticles (CuS@CS-NPs), a photothermal agent, with Paclitaxel to evaluate their combined effect on MCF-7 cell line.Methods: For this aim, CuS@CS-NPs and nanogel form of nanoparticles (CuS@CS-NGs) were obtained. Structural characterization, Particle size distribution, zeta potential and morphological analysis of the prepared nanoparticles and nanogels was done by different methods. Under Irradiation the photothermal effects of CuS@CS-NGs was measured. After encapsulation of paclitaxel to CuS@CS-NGs, release of paclitaxel from nanogels was examined. The cytotoxicity of the nanogels, Paclitaxel alone and paclitaxel encapsulated nanogels against MCF7 cell line was investigated via MTT assay in presence and absence of NIR irradiation. The apoptotic effect of them on MCF-7 cells and cellular uptake of FITC labeled nanogels in cells was determined using flow cytometry. Results: Comparing temperature alteration of different aqueous dispersions of CuS@CS-NGs showed that temperature changes increased with rising photothermal agent concentration. Paclitaxel’ entrapment efficacy into CuS@CS-NG was 96.94%±0.73, due to the chitosan layer. Compared to pH 7.4, paclitaxel release from paclitaxel encapsulated nanogel was more slow and sustained at pH 5.8. Flow cytometry results showed that nanogel alone had a 23.05% uptake rate in MCF-7 cells. The cellular absorption increased to 43.02% after Paclitaxel encapsulation. Based on MTT experiment, nanogel alone without irradiation had no cytotoxicity in cells, proving its good cytocompatibility. Paclitaxel encapsulated nanogels had more cytotoxicity than Paclitaxel or nanogel alone in cells, under irradiation.Discussion: Various tests proved successful synthesis of CuS@CS-NPs and CuS@CS-NGs. biological studies proved the better effect of combination treatment over phototherapy or chemotherapy alone.