Microfluidic synthesis and biological evaluation of photothermal biodegradable copper sulphide nanoparticles

INTRODUCTION Copper(II) sulfide(CuS) nanoparticles are semiconductor chalcogenides with electronic and optical properties. As plasmonic material, it absorbs near infrared light converting it into heat due to the excitation of... [ view full abstract ]

INTRODUCTION
Copper(II) sulfide(CuS) nanoparticles are semiconductor chalcogenides with electronic and optical properties. As plasmonic material, it absorbs near infrared light converting it into heat due to the excitation of direct and indirect transitions and plasmonic photoexcitation(1)(Smith, 2015). Those optical properties make them useful in a wide variety of biomedical applications.
Biodegradability and higher photothermal conversion efficiencies(1) are one of the main advantages of CuS nanoparticles compared to other plasmonic nanoparticles. Thus, Guo et al.,2013, demonstrated that plasmonic hollow gold NPs remained in the body one month after injection in BALB/c mice at high levels(> 96%)whereas, only a 10% of CuS NPs injected remained in the animals, being mostly excreted following the hepatobiliary route.
Polydispersity, low-yield and batch-to-batch inconsistencies are the main shortcomings when synthesizing NPs which can be overcome by using microfluidic reactors. In this work we have produced CuS NPs in a continuous process showing high photothermal efficiency as well as with the ability of generating reactive oxygen species(ROS).
METHODS
CuS NPs were synthetized using a batch reactor at different temperatures following the work of Ramadan et al.2012. The continuous microfluidic synthesis was carried out by using two consecutive Y-shaped PEEK micromixers to produce sacrificial Cu2O NPs in a first step and CuS NPs in a second step. The NPs obtained were characterized by TEM, XRD, UV-vis, XPS and DLS. Photothermal effects and ROS generation were also evaluated.
The NPs cytotoxicity and evaluation of cell apoptosis were performed on mouse mesenchymal stem cells, human dermal fibroblasts and THP1 human monocytes and macrophages.

RESULTS AND DISCUSSION
It is possible to synthesize aqueous CuS NPs in a continuous manner showing absorbance in the near infrared region of the electromagnetic spectrum with a microfluidic reactor. The NPS physicochemical properties are similar to the ones obtained in the conventional batch synthesis although the synthesis times were reduced 4 fold when using the microreactor. Under simulated physiological conditions CuS nanoparticles degrade into soluble copper sulfates which highlights the advantage of those nanomaterials compared to other conventional plasmonic nanomaterials. Those NPs show at subcytotoxic doses an elevated photothermal effect as well as ROS generation.