Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs

• Published in: Acta pharmaceutica Sinica. B Vol. 12; no. 6; pp. 2624 - 2639
• Main Authors: Li, Yamin, Ye, Zhongfeng, Yang, Hanyi, Xu, Qiaobing
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2022; Elsevier
• Subjects: Cancer therapy; Combinatorial library; Drug delivery; Gene therapy; Lipid nanoparticle; Protein delivery; Review; Protein delivery; Drug delivery; Gene therapy; Cancer therapy; Lipid nanoparticle; Combinatorial library
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2022.04.013

Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery. In this Review, we highlight our recent progress in the design, synthesis, characterization, evaluation, and optimization of combinatorial LNPs with novel structures and properties for the delivery of small- and macromolecular therapeutics both in vitro and in vivo. These delivery systems have enormous potentials for cancer therapy, antimicrobial applications, gene silencing, genome editing, and more. We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics. Lipid nanoparticles are a potent and versatile platform for the delivery of small molecule drugs, proteins, and nucleic acids, for a variety of therapeutic applications including genome editing, cancer therapy, and more. [Display omitted]