脂质纳米颗粒在肿瘤治疗中的发展及应用

The development and application of lipid nanoparticle in tumor therapy

全球恶性肿瘤的发病率逐年攀升,抗肿瘤治疗仍是世界难题。核酸药物作为一种新型治疗方法为肿瘤治疗开辟新的途径,然而其成药性受到体内递送系统的限制。脂质纳米颗粒(lipid nanoparticle,LNP)是目前最先进的非病毒递送系统。LNP包裹核酸药物并递送至靶细胞发挥有效的抗肿瘤作用,具有细胞毒性小、靶向性可控等优点,且发展潜力巨大。本综述聚焦LNP的发展,详细阐述LNP在肿瘤治疗中的临床前及临床研究进展,包括CRISPR/Cas 9系统、mRNA疫苗、小干扰RNA(small interfering RNA,siRNA)疗法以及嵌合抗原受体(chimeric antigen receptor,CAR)细胞疗法等,同时讨论了LNP进一步应用于临床治疗的挑战,旨在建立理论框架和创新设计概念,以推进更有效和安全的体内递送策略。

The global incidence of malignant tumors is increasing year by year,and anti-tumor therapy remains a difficult problem worldwide.As new therapeutic approaches,nucleic acid drugs have opened up novel avenues for oncology treatment,but their drugability is limited by in-vivo delivery systems.Lipid nanoparticle(LNP)is the most advanced non-viral delivery system available.LNP encapsulates nucleic acid drugs and delivers them to target cells for effective anti-tumor actions,with the advantages of low cytotoxicity and controllable targeting,and great potential for development.This review centers on the development of LNP technology and provides detailed insights into the preclinical and clinical advancements of LNP in cancer treatment,encompassing the CRISPR/Cas9 system,mRNA vaccine,small interfering RNA(siRNA),Chimeric antigen receptor(CAR)cell therapy,and other related modalities.Simultaneously,the challenges for further application of LNP in clinical therapy are discussed,with the aim of establishing theoretical frameworks and innovative design concepts for the advancement of more effective and secure in vivo delivery strategies.