Wang Ming, Altinoglu Sarah, Takeda Yuji S, Xu Qiaobing
Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, United States of America.
PLoS One. 2015 Nov 3;10(11):e0141860. doi: 10.1371/journal.pone.0141860. eCollection 2015.
Exosomes are small, cell-secreted vesicles that transfer proteins and genetic information between cells. This intercellular transmission regulates many physiological and pathological processes. Therefore, exosomes have emerged as novel biomarkers for disease diagnosis and as nanocarriers for drug delivery. Here, we report an easy-to-adapt and highly versatile methodology to modulate exosome composition and conjugate exosomes for intracellular delivery. Our strategy combines the metabolic labeling of newly synthesized proteins or glycan/glycoproteins of exosome-secreting cells with active azides and bioorthogonal click conjugation to modify and functionalize the exosomes. The azide-integrated can be conjugated to a variety of small molecules and proteins and can efficiently deliver conjugates into cells. The metabolic engineering of exosomes diversifies the chemistry of exosomes and expands the functions that can be introduced into exosomes, providing novel, powerful tools to study the roles of exosomes in biology and expand the biomedical potential of exosomes.
外泌体是细胞分泌的小囊泡，可在细胞间传递蛋白质和遗传信息。这种细胞间传递调节许多生理和病理过程。因此，外泌体已成为疾病诊断的新型生物标志物和药物递送的纳米载体。在此，我们报告了一种易于适应且用途广泛的方法，用于调节外泌体组成并将外泌体偶联用于细胞内递送。我们的策略将外泌体分泌细胞新合成的蛋白质或聚糖/糖蛋白的代谢标记与活性叠氮化物和生物正交点击共轭相结合，以修饰外泌体并使其功能化。整合叠氮化物的外泌体可以与多种小分子和蛋白质偶联，并能有效地将偶联物递送至细胞内。外泌体的代谢工程使外泌体的化学性质多样化，并扩展了可以引入外泌体的功能，为研究外泌体在生物学中的作用提供了新颖、强大的工具，并扩展了外泌体的生物医学潜力。
