PolyethyleneGlycolated Shikonin-Functionalized CarbonNanotubes as an Effective Anticancer System Combining Chemotherapyand Photothermal Therapy

Shikonin (SHK) is a potential chemotherapy drug for the treatment of breast cancer. However, the poor water solubility, as well as the lack of tumor targeting, restricts the practical application of SHK molecules. In addition, chemotherapy alone is no longer sufficient for current clinical treatment, and it needs to be combined with other therapeutical methods. Here, using our previously developed shikonin-disulfide bond-poly­(ethylene glycol) compound (referred to as SHK-SS-PEG) as a chemotherapy molecule that responds to reduced glutathione (GSH), a SHK-SS-PEG-functionalized multiwall carbon nanotubes (MWCNTs) system (SHK-SS-PEG/MWCNTs) was prepared by physical interaction. Such a system exhibits both chemotherapy and photothermal therapy for breast cancer. The physical adsorption of SHK-SS-PEG on the MWCNTs causes them to have good dispersion and storage stability for up to 3 months in aqueous solution and possess excellent photothermal conversion performance of MWCNTs. In addition, the drug release rate of SHK-SS-PEG/MWCNTs in MCF-7 cells as triggered by a near-infrared (NIR) laser was increased by 2-fold compared with that of nonirradiated cells. In vitro antitumor studies demonstrated that SHK-SS-PEG/MWCNTs had a combined effect of chemotherapy and photothermal therapy. The mortality of MCF-7 cells treated with SHK-SS-PEG/MWCNTs ([MWCNTs] = 75 μg/mL) under 808 nm NIR laser irradiation was as high as 87.78%, which was 34.39% and 28.31% higher than that of the SHK-SS-PEG/MWCNTs group without NIR laser irradiation and the MWCNTs group irradiated with NIR laser at the same equivalent concentration, respectively. These results indicated that SHK-SS-PEG/MWCNTs combined with an 808 nm NIR laser were an ideal antitumor system.