纳米颗粒介导的 mRNA 递呈的最佳递送策略。

Optimal delivery strategies for nanoparticle-mediated mRNA delivery.

机构信息

Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China.

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.

出版信息

J Mater Chem B. 2023 Mar 8;11(10):2063-2077. doi: 10.1039/d2tb02455a.

Abstract

Messenger RNA (mRNA) has emerged as a new and efficient agent for the treatment of various diseases. The success of lipid nanoparticle-mRNA against the novel coronavirus (SARS-CoV-2) pneumonia epidemic has proved the clinical potential of nanoparticle-mRNA formulations. However, the deficiency in the effective biological distribution, high transfection efficiency and good biosafety are still the major challenges in clinical translation of nanomedicine for mRNA delivery. To date, a variety of promising nanoparticles have been constructed and then gradually optimized to facilitate the effective biodistribution of carriers and efficient mRNA delivery. In this review, we describe the design of nanoparticles with an emphasis on lipid nanoparticles, and discuss the manipulation strategies for nanoparticle-biology (nano-bio) interactions for mRNA delivery to overcome the biological barriers and improve the delivery efficiency, because the specific nano-bio interaction of nanoparticles usually remoulds the biomedical and physiological properties of the nanoparticles especially the biodistribution, mechanism of cellular internalization and immune response. Finally, we give a perspective for the future applications of this promising technology. We believe that the regulation of nano-bio interactions would be a significant breakthrough to improve the mRNA delivery efficiency and cross biological barriers. This review may provide a new direction for the design of nanoparticle-mediated mRNA delivery systems.

摘要

信使 RNA(mRNA)已成为治疗各种疾病的新型高效药物。脂质纳米颗粒-mRNA 对新型冠状病毒(SARS-CoV-2)肺炎疫情的成功治疗证明了纳米颗粒-mRNA 制剂的临床潜力。然而,有效的生物分布、高转染效率和良好的生物安全性仍然是 mRNA 传递的纳米医学临床转化的主要挑战。迄今为止,已经构建了多种有前途的纳米颗粒,并对其进行了逐步优化,以促进载体的有效生物分布和高效 mRNA 传递。在本综述中,我们重点介绍了脂质纳米颗粒的纳米颗粒设计,并讨论了用于克服生物屏障和提高递送效率的纳米颗粒-生物学(nano-bio)相互作用的操纵策略,因为纳米颗粒的特定 nano-bio 相互作用通常会重塑纳米颗粒的生物医学和生理学特性,特别是生物分布、细胞内化机制和免疫反应。最后,我们对这项有前途的技术的未来应用提出了展望。我们相信,对 nano-bio 相互作用的调控将是提高 mRNA 传递效率和跨越生物屏障的重要突破。本综述可能为纳米颗粒介导的 mRNA 传递系统的设计提供新的方向。

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