Targeted Delivery of Nucleic Acid Therapeutics: Emerging Carriers and Applications in Common Metabolic and Inflammatory Diseases

Xiyuan Lin,1,* Li Chen,2,* Keran Jia,3,* Shengbiao Li,4 Qiuhong Li,5 Jingyan Yi,1 Jinshan Xing6 1Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Key Laboratory of Medical Electrophysiology, Ministry of Education, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Neurology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 3Department of Health Services and Management, School of Health Care Technology, Chengdu Neusoft University, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 5Department of Histology and Embryology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinshan Xing; Jingyan Yi, Email xingjinshan2020@swmu.edu.cn; jingyany@swmu.edu.cnAbstract: Recent advances in genomics and molecular biology have accelerated the development of nucleic acid-based therapeutics. To optimize their clinical efficacy, various delivery systems—including lipid nanoparticles, polymeric nanomaterials, inorganic nanoparticles (NPs), extracellular vesicles (EVs), viral vectors, protein carriers, and nucleic acid conjugates—have been explored to improve stability, cellular uptake, and bioavailability. This review provides an overview of the current state of nucleic acid therapeutics, focusing on their classification, delivery strategies, and applications in metabolic and inflammatory diseases. Emphasis is placed on the mechanisms of action, targeted delivery approaches, and the existing challenges these systems face. Literature was sourced from PubMed and Web of Science, relevance to the topic, and publication timeline (2020– 2025). The aim is to propose insights into the optimization of nucleic acid drugs and the development of novel delivery systems, offering new perspectives for the treatment of complex diseases. Keywords: nucleic acid therapeutics, delivery systems, metabolic diseases, inflammatory diseases