Physiological Barriers and Strategies of Lipid‐Based Nanoparticles for Nucleic Acid Drug Delivery

• Published in: Advanced materials (Weinheim) Vol. 36; no. 22; pp. e2303266 - n/a
• Main Authors: Hu, Mingdi, Li, Xiaoyan, You, Zhen, Cai, Rong, Chen, Chunying
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.05.2024
• Subjects: Animals; Drug Carriers - chemistry; Drug Delivery Systems - methods; Humans; Lipids; Lipids - chemistry; lipid‐based nanoparticles; Nanoparticles; Nanoparticles - chemistry; Nucleic acids; Nucleic Acids - administration & dosage; Nucleic Acids - chemistry; physiological barriers; Physiology; protein corona; Protein Corona - chemistry; strategies; lipid‐based nanoparticles; strategies; physiological barriers; protein corona
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202303266

Lipid‐based nanoparticles (LBNPs) are currently the most promising vehicles for nucleic acid drug (NAD) delivery. Although their clinical applications have achieved success, the NAD delivery efficiency and safety are still unsatisfactory, which are, to a large extent, due to the existence of multi‐level physiological barriers in vivo. It is important to elucidate the interactions between these barriers and LBNPs, which will guide more rational design of efficient NAD vehicles with low adverse effects and facilitate broader applications of nucleic acid therapeutics. This review describes the obstacles and challenges of biological barriers to NAD delivery at systemic, organ, sub‐organ, cellular, and subcellular levels. The strategies to overcome these barriers are comprehensively reviewed, mainly including physically/chemically engineering LBNPs and directly modifying physiological barriers by auxiliary treatments. Then the potentials and challenges for successful translation of these preclinical studies into the clinic are discussed. In the end, a forward look at the strategies on manipulating protein corona (PC) is addressed, which may pull off the trick of overcoming those physiological barriers and significantly improve the efficacy and safety of LBNP‐based NADs delivery. Lipid‐based nanoparticles (LBNPs) are currently the most promising delivery vehicles of nucleic acid drugs. However, their delivery efficiency and safety are largely compromised by a cascade of physiological barriers. In this review, the five different levels of physiological barriers for LBNP‐based nucleic acids delivery and the current coping strategies are discussed systematically.