Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Control Release. 2024 Jan;365:176-192. doi: 10.1016/j.jconrel.2023.11.030. Epub 2023 Nov 23.
Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of HO. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.
液-液相分离形成的凝聚液滴由于能够在保持生物活性的同时浓缩生物大分子，因此引起了相当大的关注。然而，由于凝聚液滴缺乏生理稳定性和固有的膜结构，因此将其开发为治疗药物的递送囊泡仍然具有挑战性。本文通过使用聚赖氨酸-多核苷酸复合物凝聚液滴来高效且简便地浓缩小分子、生物大分子和纳米颗粒，而无需有机溶剂。为了提高生物相容性，进一步在凝聚液滴表面涂覆聚乙二醇化磷脂膜，以制备具有类似膜和细胞质结构的凝聚液滴基人工原细胞（ArtPC）。ArtPC 可以将尿酸酶和过氧化氢酶的循环催化系统限制在内部，以降解尿酸并耗尽 HO 的毒性。这种具有生物功能的 ArtPC 可有效降低持续高尿酸血症小鼠的血液尿酸水平并防止肾脏损伤。基于 ArtPC 的治疗方法可以连接合成生物学、药剂学和治疗学等多个学科。
