Photothermal photodynamic therapy and enhanced radiotherapy of targeting copolymer-coated liquid metal nanoparticles on liver cancer.

The maximized therapeutic efficacy in tumor treatment can be achieved with combination therapy. Herein, a metronidazole (MN) and RGD peptides were linked with the copolymer chains of polyacrylic acid (PAA) and polyethylene glycol (PEG) by condensation and Michael addition reactions, respectively, named as RGD-PEG-PAA-MN. Subsequently, liquid-metal (LM) nanoparticles broken by ultrasonication were coated with modified copolymer, forming RGD-PEG-PAA-MN@LM nanoparticles. These nanoparticles with the degradation under an acidic condition could target to tumor cells, and LM of these composited nanoparticles could not only efficiently convert the photoenergy of near infrared (NIR) into thermal energy, but also produce more reactive oxygen species under NIR or X ray irradiation. Furthermore, MN in the composited nanoparticles could enhance their radiation sensitivity of tumor tissues with hypoxia condition. The synergic effect of these nanoparticles on cancer limitation after the sequential radiations of NIR and X ray was significantly higher than the single radiation. In the experiments of tumor bearing mice, the volume of the tumor in RGD-PEG-PAA-MN@LM group at 14th day after two radiations of NIR and X-ray were significantly smaller than LM group, and the tumor of RGD-PEG-PAA-MN@LM group at 14th day after two radiations almost disappeared, suggesting better synergistic effect of RGD-PEG-PAA-MN@LM nanoparticles on photothermal conversion, photodynamics under two irradiations and their enhanced sensitization of X-ray radiation. Our results indicated that the prepared nanoparticles would be applied in the combinational therapy of liver tumor by the photothermal, photodynamic and sensitized radiation.