Drug-loaded copper sulfide nanoparticles with high photothermal conversion and pH-stimuli response for drug delivery

Abstract

In recent years, the incidence of malignant tumors is increasing year by year. Therefore, new antitumor drugs and treatment modalities are urgently needed. While, the biggest challenge to oncology drugs is to treat tumors in a safe and effective manner. Currently, most of the cancer patients in treatment are suffering due to side effects of oncology drugs. In order to reduce negative effects of tumor drugs, formulations of multifunctional nanocarriers have attracted attention because of their significant biological activity without damage to normal cells. These include formulations such as drug-loaded silica nanoparticles, photothermal treatment of gold nanoparticles, photodynamic therapy of copper sulfide nanoparticles and other multifunctional nanocomposites. In this study, a novel kind of high photothermal conversion CuS NPs as a pH-sensitive drug release system is going to be introduced. Firstly, CuS NPs with a uniform particle size was prepared by copper ions and sulfur ions in solution. Secondly, the PDA was modified on the surface of CuS NPs and DOX was adsorbed on the outside of PDA via non-covalent self-assembly. Finally, a drug-loaded core-shell nanoparticle DOX@CuS/PDA was obtained, with the core of CuS NPs and the shell of PDA. Further studies on DOX@CuS/PDA were performed to verify its anti-cancer effect. Surface morphology of DOX@CuS/PDA was observed by transport electronic microscope (TEM). TEM images show that DOX@CuS/PDA is uniform with a size of 70± 10 nm and appears as a spherical shape with a CuS NPs core. After comprehensive consideration of absorbance test, wavelength penetration capability and equipment, 808 nm near-infrared light was considered to be the most suitable light source. The 200 μg/mL of CuS NPs solution was heated to 54°C in 120 s under the irradiation of 808 nm near-infrared light with a power of 1 W/cm2, and the photothermal conversion rate was as high as 34.2%. The temperature of DOX@CuS/PDA was raised to 41.4°C in the same condition. In vitro release assay, the cumulative release of DOX at 72 h in the environment of pH 5.0 was 6 times higher than that of pH 7.4, which proves that DOX@CuS/PDA possesses a significant pH-stimulation response mechanism. Interestingly, DOX is adsorbed on the surface of the PDA through non-covalent self-assembly. When DOX@CuS/PDA stimulated by weak acid environment, this state of non-covalent self-assembly is undermined and the DOX is released. The mechanism of drug loading and pH response release was introduced in details. In the cancer cell experiments of DOX@CuS/PDA in vitro , the survival rate of cancer cells is 27%−33%, which effectively enhances the killing effect of tumor cells. It shows that the combination of advertising heat therapy and chemotherapy has good synergy, through the calculation of coordination coefficient. CuS NPs converts light energy into heat energy under 808 nm near-infrared lights to kill tumor cells by thermal effect and the DOX in DOX@CuS/PDA will accelerate release in a weak acid environment of tumor site. Tumor cells can be effectively killed by combining photothermal therapy with drug therapy. From the above, a novel research is put forward in this study for the combination of photothermal therapy and chemotherapy and provides a new understanding of drug-loaded by adsorption and pH-stimuli response.