Co-loading of photothermal agents and anticancer drugs into porous silicon nanoparticles with enhanced chemo-photothermal therapeutic efficacy to kill multidrug-resistant cancer cells.

Abstract

The development of nanoparticles-based drug delivery systems with a high therapeutic efficacy is necessary to treat multidrug-resistant (MDR) cancer cells. Herein, photothermal agents (IR820 dyes) and anticacner drugs (doxorubicin, DOX) were successively incorporated into amino-terminated porous silicon nanoparticles (NH2-PSiNPs) via electrostatic attractions, to prepare DOX/IR820/NH2-PSiNPs nanocomposites with a high loading amount of DOX (13.3%, w/w) and IR820 (18.6%, w/w), respectively. Meanwhile, DOX molecules were also directly loaded into NH2-PSiNPs to form DOX/NH2-PSiNPs nanocomposites (DOX, 18.7%, w/w). Compared with low release percentage (20.3%) of DOX molecules from DOX/NH2-PSiNPs in acidic environments under NIR laser irradiation, DOX/IR820/NH2-PSiNPs had dual pH/NIR light-triggered release and their release percentage could reach 88.1% under the same conditions. Furthermore, cellular interactions tests demonstrated that DOX/IR820/NH2-PSiNPs could delivery more DOX molecules into the nuclei of MDR cancer cells, with efficient intracellular release triggered by NIR light, in contrast to DOX/NH2-PSiNPs. Finally, DOX/IR820/NH2-PSiNPs exhibited an enhanced chemo-photothermal therapeutic efficacy (cell viability, 38.4%) of killing MDR cancer cells in vitro, compared with 85.4% of free DOX and 75.9% of DOX/NH2-PSiNPs. Therefore, based on PSiNPs-based nanocarriers conjugated with photothermal agents and anticancer drugs, NIR light-triggered drug delivery system with higher efficacy of combined chemo-photothermal therapy would have important potential on MDR cancer treatments in future.