Li Yamin, Ye Zhongfeng, Yang Hanyi, Xu Qiaobing
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Acta Pharm Sin B. 2022 Jun;12(6):2624-2639. doi: 10.1016/j.apsb.2022.04.013. Epub 2022 Apr 27.
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 and 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 and . 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.
基于脂质纳米颗粒（LNP）的药物递送系统已成为临床上最先进的非病毒递送技术。LNP 可以封装和递送多种生物活性剂，包括小分子药物、蛋白质和肽以及核酸。然而，由于小分子和大分子货物的物理化学性质可能有很大差异，每个 LNP 载体系统都需要仔细定制，以便以安全有效的方式递送货物分子。我们团队应用组合文库合成方法和筛选策略来开发用于药物递送的 LNP 递送系统。在这篇综述中，我们重点介绍了我们在设计、合成、表征、评估和优化具有新颖结构和性质的组合 LNP 方面的最新进展，这些 LNP 用于递送小分子和大分子治疗剂。这些递送系统在癌症治疗、抗菌应用、基因沉默、基因组编辑等方面具有巨大潜力。我们还讨论了新型 LNP 疗法的机制研究和临床转化面临的关键挑战。
