Self-assembled pH-responsive DNA nanosponges for targeted co-delivery of doxorubicin and capsaicin for colorectal cancer therapy

DNA nanostructures have been engineered into various delivery systems for anti-cancer chemotherapy. However, these nanostructures are hindered in their therapeutic applications due to their inability to co-deliver drugs, weak biostability, the large size of the delivery system, and the high cost of production. In this study, we developed a pH-controlled-release delivery system to target co-deliver Dox and CAPs solely to CRC cells. RCA technology produced high quantities of DNA-NS, which were then condensed with PEI. PEI shrank the size of DNA-NS from 1617 nm to 342 nm. Our novel delivery system intercalated the two drugs with a high loading efficiency of 78% at a ratio Dox to CAPs ratio of 1.16:1, which released less than 20% of the drugs at pH 7.4. AS1141 functional sites on DNA-NS efficiently facilitated higher cellular update and aided the DNA-NS/PEI to bond selectively to SW480 cells via the surface-expressed nucleolin. Dox and CAPs combinations had DRI scores >1 and CI scores <1, indicating synergism. The two drug combinations loaded onto the DNA-NS synergistically inhibited SW480 cell proliferation, induced intracellular ROS burst, and decreased mitochondrial membrane potential. These results show that the novel delivery system could be promising in biomedical applications.