BSA-based Cu₂Se nanoparticles with multistimuli-responsive drug vehicles for synergistic chemo-photothermal therapy

Functionalized-nanoparticles have been developed as novel therapeutic delivery platform for simultaneous drug loading and therapy over the past decade. Rationally-designed biocompatible nanosystem simultaneously with multistimuli-responsive property and synergistic therapeutic potential are highly desirable for modern biological applications. Herein, Cu₂Se nanoparticles (Cu₂SeNPs) with suitable size have been functionalized by bull serum albumin (BSA) through a simply, facile and controllable method. As a result, Cu₂SeNPs modified by BSA (BSA-Cu₂SeNPs) showed excellent biocompatibility and stability. The strong absorbance of BSA-Cu₂SeNPs at near infrared region imparts them with high photothermal efficiency. Then loading doxorubicin (DOX, anticancer drug) on the surface of BSA-Cu₂SeNPs, and consequently, a novel multifunctional nanosystem of BSA-Cu₂SeNPs-DOX is designed. The BSA-Cu₂SeNPs can achieve high DOX loading capacity (approximately 157 μg DOX per mg of Cu₂Se). Furthermore, a rational and precise release of DOX from the BSA-Cu₂SeNPs-DOX could be easily realized under the stimulates of the pH and temperature, which remarkably improved antitumor efficacy of combined chemotherapy and photothermal therapy triggered by 808 nm NIR laser. Thus, the BSA-Cu₂SeNPs-DOX could serve as an ideal nanoplatform for cancer diagnosis and treatment in future. The results of cell experiments show that the BSA-Cu₂SeNPs-DOX exhibited favorable selective cellular uptake cells. Under the NIR laser irradiation, BSA-Cu₂SeNPs-DOX could induce the excessive expression of ROS, eventually leading to the death of U251 cells. Both in vitro and in vivo experiments indicate that the nanosystem of BSA-Cu₂SeNPs-DOX showed excellent synergistic therapeutic effect and multistimuli-responsive drug vehicle, which will exert huge potential for future clinical application.