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聚合介导的活细胞多功能化用于增强基于细胞的治疗。

Polymerization-Mediated Multifunctionalization of Living Cells for Enhanced Cell-Based Therapy.

机构信息

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Department of Ophthalmology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China.

出版信息

Adv Mater. 2021 Apr;33(13):e2007379. doi: 10.1002/adma.202007379. Epub 2021 Feb 25.

DOI:10.1002/adma.202007379
PMID:33629757
Abstract

Surface decoration of living cells by exogenous substances offers a unique tool for understanding and tuning cell behaviors, which plays a critical role in cell-based therapy. Here, a facile yet versatile approach for decorating individual living cells with multimodal coatings is reported. By simply co-depositing with dopamine under a cytocompatible condition, various functional small molecules and polymers can be encoded to form a multifunctional coating on a cell's surface. The accessibility and versatility of this method to decorate diverse cells, including bacteria, fungi, and mammalian cells is demonstrated. With the ability to tune surface functions, ligand co-deposited gut microbiota is prepared as oral therapeutics for targeted treatment of colitis. Given the dual cytoprotective and targeting effects of the coating, decorated cells show more than 30-times higher bioavailability in the gut and fourfold higher accumulation in the inflamed tissue in comparison with those of uncoated bacteria. Multimodal therapeutic cells further validate strikingly increased treatment efficacy over clinical aminosalicylic acid in colitis mice. Decorating with multifunctional coatings proposes a robust platform for developing multimodal cells for enhanced cell-based therapy.

摘要

通过外源物质对活细胞进行表面修饰为理解和调控细胞行为提供了一种独特的工具,这在基于细胞的治疗中起着至关重要的作用。在这里,我们报道了一种简单而通用的方法,可将多种模式的涂层修饰到单个活细胞上。通过在细胞相容条件下与多巴胺简单共沉积,可以将各种功能的小分子和聚合物编码到细胞表面的多功能涂层上。该方法具有修饰多种细胞的可及性和通用性,包括细菌、真菌和哺乳动物细胞。通过调节表面功能,我们制备了负载配体的肠道微生物群作为口服治疗剂,用于靶向治疗结肠炎。鉴于涂层的双重细胞保护和靶向作用,与未涂层的细菌相比,经过修饰的细胞在肠道中的生物利用度提高了 30 多倍,在炎症组织中的积累增加了 4 倍。多功能治疗细胞进一步验证了在结肠炎小鼠中治疗效果明显优于临床用的氨基水杨酸。用多功能涂层进行修饰为开发用于增强基于细胞的治疗的多功能细胞提供了一个强大的平台。

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