An Ultrasound-Triggered ROS Sustained Supplier Based on Open Source and Reduce Expenditure Strategy for Colon Cancer Therapy

The reactive oxygen species (ROS) play a decisive role in sonodynamic therapy (SDT). However, hypoxic microenvironment of tumors and short lifetime of ROS limit the implementation of SDT. In this work, an ultrasound (US)-triggered ROS sustained supplier based on open source and reduce expenditure strategy was constructed. The mesoporous titanium dioxide nanoparticles (MTN) were used as carriers and sonosensitizers, to load US-responsive perfluoropentane (PFP) and bleomycin (BLM), a blocking agent to reduce ROS scavenging. Thereafter, nanoparticles were wrapped by red blood cell membrane (RBCm) with TKD modification (TKD@RMPB). Under US irradiation, MTN disintegrated into small TiO2 nanoparticles to release PFP and BLM. PFP effectively supplied O-2 to enhance ROS generation. Furthermore, BLM reduced the activity of SOD enzyme so that ROS clearance would decrease. This dual role contributed ROS explosive accumulation in tumor cells. In vitro results showed the ROS level of TKD@RMPB group was 3.62 times that of MTN group. Compared with MTN, the proportion of DNA damage in TKD@RMPB group increased by 2.23 times. Moreover, in vivo results indicated that TKD@RMPB could significantly reduce pulmonary fibrotic lesions caused by BLM, suggesting that TKD@RMPB realized simultaneous chemotherapy and SDT for HT-29 colon cancer with high efficiency and low toxicity.