Multi-layered tumor-targeting photothermal-doxorubicin releasing nanotubes eradicate tumors in vivo with negligible systemic toxicity

Abstract

Multi-layered single-walled carbon nanotubes, termed SWNT@BSA@Au-S-PEG-FA@DOX, which integrate photothermal therapy with small molecule drug delivery, were prepared using a facile layer-by-layer assembly process. Oxidized and cut single-walled carbon nanotubes (SWNTs) were coated with bovine serum albumin (BSA) to provide abundant active sites for the nucleation of Au seeds, which are subsequently converted into gold nanoparticles (Au NPs) by in situ reduction. The resulting SWNT@BSA@Au material exhibits ideal photothermal properties. Further modification of the nanomaterial with folic acid terminated-polyglycol (FA-PEG-SH) and subsequent loading with doxorubicin (DOX) afford the SWNT@BSA@Au-S-PEG-FA@DOX. The FA terminated PEG endows the material with high water-dispersibility, biocompatibility and cancer cell selectivity. A high drug loading ratio for DOX of up to 590% was achieved, with the drug release being pH and temperature dependent, adding to the selectivity of the system. High efficacy of the SWNT@BSA@Au-S-PEG-FA@DOX material, when combined with photothermal therapy (irradiation of the tumor with an 808 nm laser, 1 W cm⁻² for 5 min, 24 h after systemic injection of the nanomedicine), was demonstrated in vivo, resulting in complete tumor eradication. Remarkably, the side effects are negligible with only minor damage to normal tissues including the liver and kidneys being observed.