Aptamer and phosphorothioated DNA engineered liposomes as a targeted intracellular protein delivery system

Targeted delivery of proteins into desired cell groups is crucial for disease therapy and cellular functionalization. However, current delivery methods face severe side effects and off-target problems, making it difficult to achieve cell-targeted protein delivery. Herein, we developed a user-friendly membrane fusion liposome for cancer cell-targeted protein delivery. Phosphorothioated DNA-mediated membrane fusion was employed as an efficient transmembrane delivery approach. The phosphorothioated DNA was capped with the AS1411 aptamer, which specifically recognizes nucleolar proteins on the cancer cell membrane, enabling a controllable delivery of proteins into targeted cancer cells. This delivery system exhibited commendable biocompatibility and targeted delivery ability, thereby realizing highly effective cancer cell inhibition in vitro. The in vivo results further suggested that the membrane protein-responsive membrane fusion delivery system offers a new avenue for highly biocompatible and targeted protein delivery.