Delivery of Antisense Oligonucleotides Using the Nano‐Cell Vesicle Technology System (nCVTs) for Targeted Cancer Therapy

Abstract Nucleic acid therapeutics (NATs) promise to revolutionize the fight against diseases like cancer, yet their full potential remains untapped due to significant delivery challenges. In this study, innovative nano‐cell vesicle technology systems (nCVTs) are developed to target NATs to cancer cells. nCVTs are created by fusing cationic lipids with pre‐emptied cell membranes that can efficiently bind and transport NATs such as antisense oligonucleotides (ASOs). In the study, nCVTs loaded with an anti‐cancer ASO, AS014 (nCVTs _AS014 ) outperformed both liposomes and free AS014 in delivering the therapeutic payload into cancer cells, reaching both the cytoplasm and nuclei with remarkable efficiency while displaying lower intrinsic cytotoxicity. Most impressively, nCVTsAS014 demonstrated potent inhibition of tumor growth in vivo, underscoring its potential as a powerful cancer therapy platform. Altogether, the findings highlight nCVTs as a promising strategy to unlock the therapeutic power of NATs, paving the way toward more effective and targeted treatments for cancer.