Wang Yueji, Bo Yang, Liu Yusheng, Zhou Jiadiao, Nguyen Daniel, Baskaran Dhyanesh, Liu Yuan, Wang Hua
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biomater Sci. 2025 Jan 14;13(2):434-445. doi: 10.1039/d4bm01352b.
Adipocytes play a critical role in energy storage and endocrine signaling and are associated with various diseases such as cancer and diabetes. Facile strategies to engineer adipocytes have long been pursued for elucidating adipocyte biology and developing adipocyte-based therapies. Herein, we report metabolic glycan labeling of adipocytes and subsequent targeted modulation of adipocytes click chemistry. We show that azido tags expressed on the surface of adipocytes can persist for over 4 days. By conjugating dibenzocyclooctyne (DBCO)-cargos onto azido-labeled adipocytes click chemistry, the cargos can be retained on the adipocyte membrane for over 12 hours. We further show that signaling molecules including adiponectin, calreticulin, mannose-binding lectin 2, and milk fat globule-EGF factor 8 protein can be conjugated to adipocytes to orchestrate their phagocytosis by macrophages. The azido-labeled adipocytes grafted into mice can also mediate targeted conjugation of DBCO-cargos . This adipocyte labeling and targeting technology will facilitate the development of adipocyte-based therapies and provides a new platform for manipulating the interaction between adipocytes and other types of cells.
脂肪细胞在能量储存和内分泌信号传导中发挥着关键作用，并与多种疾病如癌症和糖尿病相关。长期以来，人们一直在寻求简便的策略来改造脂肪细胞，以阐明脂肪细胞生物学并开发基于脂肪细胞的疗法。在此，我们报告了脂肪细胞的代谢聚糖标记以及随后通过点击化学对脂肪细胞进行靶向调控。我们表明，脂肪细胞表面表达的叠氮标签可以持续超过4天。通过点击化学将二苯并环辛炔（DBCO）-货物缀合到叠氮标记的脂肪细胞上，货物可以在脂肪细胞膜上保留超过12小时。我们进一步表明，包括脂联素、钙网蛋白、甘露糖结合凝集素2和乳脂肪球-表皮生长因子8蛋白在内的信号分子可以与脂肪细胞缀合，以协调巨噬细胞对它们的吞噬作用。移植到小鼠体内的叠氮标记脂肪细胞也可以介导DBCO-货物的靶向缀合。这种脂肪细胞标记和靶向技术将促进基于脂肪细胞的疗法的发展，并为操纵脂肪细胞与其他类型细胞之间的相互作用提供一个新平台。
