Hossainy Samir, Kang Seounghun, Gómez Medellín J Emiliano, Alpar Aaron T, Refvik Kirsten C, Ma Yvonne Yoyo, Vuong Ivan, Chang Kevin, Wang Thomas, Solanki Ani, Rowan Stuart J, Hubbell Jeffrey A
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
Department of Chemical and Biomolecular Engineering, New York University, New York, NY, USA.
Nat Biomed Eng. 2025 Aug 6. doi: 10.1038/s41551-025-01469-7.
Versatile technologies that can deliver both RNA and protein payloads could streamline development, simplify manufacturing and expand the capabilities of combination therapies. Here we demonstrate an efficient approach to forming ca. 100 nm polymer vesicles (polymersomes) capable of rapid self-assembly without organic solvents, avoiding the need for post-encapsulation purification. Block copolymers are designed with a lower critical solution temperature that renders them soluble in aqueous medium under standard refrigeration, but they spontaneously assemble at room temperature into large batches of nanoparticles with predictable size and morphology. The nanomaterials are designed with charged and biofunctional moieties to drive payload affinity and in vivo targeting, while both siRNA and proteins can be encapsulated during warming at >75% loading efficiencies. Formulations can be stored in a dry state for greater hydrolytic stability under standard refrigeration and can be diluted directly from the vial, bypassing the need for purification required for high scalability. We use our system for in vivo delivery in protein subunit vaccination, immune tolerance induction and siRNA interference therapy in cancer.
能够递送RNA和蛋白质载荷的多功能技术可以简化研发过程、简化制造流程并扩展联合疗法的能力。在此，我们展示了一种高效的方法，可形成约100纳米的聚合物囊泡（聚合物osomes），该囊泡能够在无有机溶剂的情况下快速自组装，无需进行封装后纯化。嵌段共聚物被设计成具有较低的临界溶液温度，使其在标准冷藏条件下可溶于水性介质，但在室温下会自发组装成大量具有可预测尺寸和形态的纳米颗粒。这些纳米材料被设计带有带电和生物功能部分，以驱动载荷亲和力和体内靶向性，同时在升温过程中，siRNA和蛋白质都能以>75%的装载效率进行封装。制剂可以在干燥状态下储存，以在标准冷藏条件下具有更高的水解稳定性，并且可以直接从小瓶中稀释，无需高扩展性所需的纯化步骤。我们将我们的系统用于蛋白质亚基疫苗接种、免疫耐受诱导和癌症中的siRNA干扰治疗的体内递送。
