Affiliation:
1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology Beijing 100190 China
2. Sino‐Danish College University of Chinese Academy of Sciences Beijing 100049 China
3. Sino‐Danish Center for Education and Research Beijing 100049 China
4. The GBA National Institute for Nanotechnology Innovation Guangzhou 510700 China
Abstract
AbstractLipid‐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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Beijing Nova Program
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
3 articles.
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