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双块共聚合物向性脂质纳米颗粒:下一代核酸输送系统,由封闭式阻塞喷射混合器生产

Bumjun Kim¹, Sai Nikhil Subraveti¹, Jason X Liu¹

¹Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.

ACS applied bio materials

|October 31, 2024

概括

可生物降解的区块共聚合物在纳米颗粒中取代脂质-PEG,以增强外肝核酸的输送. 这些新型纳米粒子显示了改进的转染效率和有针对性的输送,克服了当前脂质纳米粒子的局限性.

科学领域:

生物技术是生物技术.
材料科学材料科学材料科学
基因治疗基因治疗

背景情况:

脂质纳米颗粒 (LNP) 对核酸输送具有前景,但由于快速清除,在肝外输送方面面临挑战.
脂质聚乙烯甘醇 (PEG) 在血液中的快速脱离限制了LNP在肝脏之外的有效性.

研究的目的:

开发和优化可生物降解块共聚物 (BCP) 稳定型LNP (BCP-LNP) 作为传统脂质-PEG LNP的替代品.
评估BCP-LNPs用于核酸输送的物理化学性质,转染效率和准能力.

主要方法:

使用实验设计 (DOE) 方法系统优化BCP-LNP配方.
评估了HeLa和A549细胞中的物理化学特性,封装效率和转染效率.
使用Cetuximab对EGFR过度表达细胞的结合制造了向的BCP-LNP.

主要成果:

优化的BCP-LNP表现出理想的物理化学特性和高封装效率.
某些BCP-LNP配方在HeLa细胞中实现了高达40倍的转染效率,细胞毒性最小.
与非向的BCP-LNP相比,向的BCP-LNP在EGFR过度表达的A549细胞中的转染率高出2.4倍.
BCP-LNP证明了其多功能性,有效地封装和传递mRNA和等离子体DNA (pDNA).

结论:

BCP-LNP为有效的核酸输送提供了一个可行的多功能平台,克服了传统LNP的局限性.
使用可生物降解的块共聚合物增强了LNP的定,并使得更好的肝外和有针对性的输送.
对于先进的基因疗法应用,BCP-LNP具有显著的潜力,特别是对于瘤等具有挑战性的标.

关键词:

区块共聚合物区块共聚物设计实验的设计.闪光纳米降水脂质纳米粒子脂质纳米粒子它们是mRNARNA.塑体 DNA DNA 的 DNA .

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