Lapatinib (LPT)-loaded gold nanorods and pegylated gold nanorods were synthesized in this work with the long-term aim to develop a nanomedicine which will combine photothermal and pharmacological activities for a more efficient treatment of HER2 positive cancers.

Gold nanorods (GNRs) were synthesized using an aqueous seeded method and pegylated through a ligand exchange process with PEG thiol (SHPEG) with 2kDA or 6 kDa molecular weight. The morphology and size of the synthesized nanorods were investigated by transmission electron microscopy (TEM). The photothermal effect of synthesized GNRs was evaluated by irradiating different concentrations of the nanorods in water with laser NIR light (808 nm) and recording the temperature of nanorods dispersions. The colloidal stability of the nanorods was evaluated in DMEM cell culture medium and in human blood plasma as well as after storage at room temperature for different time periods. The biocompatibility of blank nanorods was evaluated by hemocompatibility (hemolysis) and cytotoxicity tests. The effect of pronase and laser light irradiation on the in vitro release profiles of LPT were investigated. Cellular uptake and cytotoxicity of the synthesized nanorods were studied in breast cancer cell lines overexpressing and not HER2 using flow cytometry and the MTT assay, respectively.

The nanorods exhibited high photothermal activity and laser irradiation of nanorods increased significantly the temperature of the surrounding medium. Both the pegylated and non-pegylated nanorods exhibited low rate of LPT release, which was significantly accelerated in the presence of pronase or under the influence of NIR laser light (808 nm) irradiation. The pegylated blank nanorods exhibited higher colloidal stability and hemocompatibility and lower cytotoxicity than the non-pegylated nanorods. The combined application of LPT-loaded nanorods and laser irradiation gave significantly higher cytotoxicity against the SK-BR-3 HER2 positive cancer cells compared to laser irradiation or LPT-loaded nanorods alone.

The combined application of laser irradiation and LPT-loaded gold nanorods exhibited higher anticancer activity against a HER2 positive cancer cell line compared to the respective monotherapies and can, thus, be considered a promising approach for a more efficient treatment of HER2 overexpressing cancers.