Biomimetic redox-responsive prodrug micelles with diselenide linkage for platinum nanozymes augmented sonodynamic/chemo combined therapy of colon cancer

Abstract

Due to the complexity of tumorigenesis, it is hard to completely cure tumors with a single tumor therapy. Combined sonodynamic therapy and chemotherapy (sono-chemotherapy) based on the stimulus-responsive nano-delivery system is a prospective antitumor strategy that has demonstrated synergistic treatment effects and higher treatment effects than any monotherapy. The multiple diselenide linkages-contained DSeDP-alt-PEG conjugated with Ce6/PTX to yield prodrugs DC and DP micelles, and platinum nanozymes that possessed multiple enzyme activities were loaded in DC to form stable micelles (DC@Pt). The nanomicelles were modified with the homologous tumor cell membrane (DPC@Pt@M) to generate a REDOX-responsive bionic nanoplatform to realize the sono-chemotherapy combined treatment for colon cancer. As a redox-responsive nanoplatform, DPC@Pt@M exhibited excellent water solubility and bioavailability, and good targeting ability both in vitro and in vivo to realize the controlled release of Ce6 and PTX at the tumor site. Pt nanozymes acted as a cascade catalyst (SOD-CAT, SOD-POD) to alleviate hypoxia and improve SDT. Under ultrasonic irradiation, the novel micelle DPC@Pt@M increased ROS production and induced apoptosis efficiently in vitro and in vivo to improve sono-chemotherapeutic efficiency for colon cancer. Therefore, sonodynamic/chemo therapies demonstrated a clear synergistic effect, and this research is expected to provide a paradigm of combination therapy strategies for colon cancer.