The deficiency of reactive oxygen species (ROS) is the main reason for the current poor efficiency of tumor photodynamic therapy (PDT). To solve this problem, a simple light-triggered core-satellite nanoplatform (UPSD@Au) has been developed by loading Au nanoparticles on the surface of mesoporous silica-coated upconversion nanoparticles. Small molecules DC50 (C17H14BrF2N3OS) and photosensitizer (silicon phthalocyanine dihydroxide, SPCD) were loaded into the silica shell to improve ROS production. Meanwhile, PDT can be triggered through facile near-infrared laser irradiation given the occurrence of a moderate photothermal transfer process between upconversion nanoparticles and Au. The reasonable increment in temperature induced by Au resulted in the timely release of DC50. The inhibition of copper transfer by DC50 results in reduced ROS scavenging and thus improves light-triggered ROS accumulation. Notably, the expression levels of the human copper-trafficking proteins Atox1 and CCS in cancerous cells exceed those in normal cells, and thus enhanced ROS accumulation effect was achieved in cancerous cells. In vitro and in vivo results demonstrate that the synergism between DC50 and SPCD coloaded in the UPSD@Au nanoplatform increases the efficiency of PDT. The UPSD@Au platform represents an efficient codelivery method for hydrophobic small molecules and improves sensitization to specific cancer therapy.
Keywords: accumulation effect of ROS; codelivery; copper transfer; photodynamic therapy; synergy efficiency.