浙江大学顾臻团队报道了通过液-液相分离组装的凝聚囊泡改善了生物药物的输送。相关研究成果于2025年1月13日发表在《自然—化学》。

囊泡在细胞物质储存和信号运输中起着至关重要的作用，甚至在细胞器和细胞的形成中也是如此。天然囊泡由脂质层组成，脂质层形成膜，用于包裹内部物质。

该文中，研究人员报告了一种由胆固醇修饰的DNA和组蛋白的液液相分离形成的凝聚囊泡。与磷脂基膜结合囊泡不同，凝聚囊泡表面没有膜结构，由高密度液体层和充水腔组成。通过一个简单的凝聚过程证明了各种生物制剂，包括病毒颗粒、mRNA、细胞因子和肽，可以在液相中无害地直接富集。

与易于聚集的液滴状凝聚层相比，凝聚层囊泡显示出优异的动力学稳定性，使其成为生物制药的多功能递送载体。证实研究，将溶瘤病毒掺入这些凝聚囊泡中，可以赋予它们强大的溶瘤功效，并在小鼠模型中引发强有力的抗肿瘤免疫反应。

附：英文原文

Title: Coacervate vesicles assembled by liquid–liquid phase separation improve delivery of biopharmaceuticals

Author: Wen, Ping, Huang, Hanwei, Zhang, Ruizhe, Zheng, Hanqi, Liang, Tingxizi, Zhuang, Chuyue, Wu, Qing, Wang, Junxia, Liu, Feng, Zhang, Ke, Wu, Wei, He, Kaixin, Liu, Funan, Li, Hongjun, Gu, Zhen

Issue&Volume: 2025-01-13

Abstract: Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid–liquid phase separation of cholesterol-modified DNA and histones. Unlike a phospholipid-based membrane-bounded vesicle, a coacervate vesicle lacks a membrane structure on the surface and is organized with a high-density liquid layer and a water-filled cavity. Through a straightforward coacervation process, we demonstrate that various biological agents, including virus particles, mRNA, cytokines and peptides, can be innocuously and directly enriched in the liquid phase. In contrast to the droplet-like coacervates that are prone to aggregation challenges, coacervate vesicles display superior kinetic stability, positioning them as a versatile delivery vehicle for biopharmaceuticals. We validate that incorporating oncolytic viruses into these coacervate vesicles endows them with potent oncolytic efficacy and elicits robust anti-tumour immune responses in mouse models.

DOI: 10.1038/s41557-024-01705-8

Source: https://www.nature.com/articles/s41557-024-01705-8