Chemo-photothermal therapy of cancer cells using gold nanorod-cored stimuli-responsive triblock copolymer

Abstract

Light-based therapies including photothermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of photothermal therapy and chemotherapy, when carefully planned, has been shown to be an effective cancer treatment option clinically and preclinically. According to these facts, gold nanorod-cored biodegradable micelles were prepared by coating gold nanorods (GNRs) with a synthesized stimuli-responsive thiol-end capped ABC triblock copolymer [poly(acrylic acid)-b-poly(N-isopropylacrylamide)-b-poly(ε-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH]. Furthermore, the anti-cancer drug doxorubicin (DOX) was conjugated onto the gold nanorod-cored micelles (GNR@polymer) by electrostatic force and the nanocomposites formed were named GNR@polymer–DOX. The success of the coating was investigated by means of thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy, as well as dynamic light scattering (DLS), and zeta potential (ξ) measurements. DOX-loading capacity and stimuli-responsive drug release ability of the synthesized nanocomposites were also investigated. The in vitro therapy effect was comprehensively evaluated among free DOX, GNR@polymer, and GNR@polymer–DOX, with or without NIR light irradiation (1064 nm, 137 mJ per pulse, 3 min) to improve the curative effect of GNR@polymer–DOX led by the combination of chemotherapy and photothermal therapy.