Hui-yan Ding,1– 3,* Han Zhou,4,5,* Yi Jiang,1,2,* Si-si Chen,6,* Xiao-xia Wu,1,2 Yang Li,1,2 Jun Luo,1,2 Peng-fei Zhang,7 Yi-nan Ding1,2 

1Department of Interventional Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang, 310022, People’s Republic of China; 2Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China; 3Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, People’s Republic of China; 4School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 5University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 6Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 7Institutes of Biomedical Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, 010020, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi-nan Ding, Department of Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China, Email dingyinanwl@126.com Peng-fei Zhang, Institutes of Biomedical Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, 010020, People’s Republic of China, Email zpf1990@ustc.edu.cn

Abstract: Cancer remains a leading cause of mortality worldwide, accounting for approximately 10 million deaths annually. Standard treatments, including surgery, radiotherapy, and chemotherapy, often result in damage to healthy cells and severe toxic side effects. In recent years, antisense technology therapeutics, which interfere with RNA translation through complementary base pairing, have emerged as promising approaches for cancer treatment. Despite the availability of various antisense oligonucleotide (ASO) drugs on the market, challenges such as poor active targeting and susceptibility to clearance by circulating enzymes remain. Compared with other delivery systems, lipid nanovesicle (LNV) delivery systems offer a potential solution that uniquely enhances ASO targeting and stability. Studies have shown that LNVs can increase the accumulation of ASOs in tumor sites several-fold, significantly reducing systemic toxic reactions and demonstrating increased therapeutic efficiency in preclinical models. Additionally, LNVs can protect ASOs from enzymatic degradation within the body, extending their half-life and thus enhancing their therapeutic effects. This paper provides a comprehensive review of recent examples and applications of LNV delivery of ASOs in cancer treatment, highlighting their unique functions and outcomes. Furthermore, this paper discusses the key challenges and potential impacts of this innovative approach to cancer therapy.

Keywords: cancer therapy, antisense oligonucleotides, lipid nanovesicles, liposomes, extracellular vesicles, cell membrane vesicles