生物正交化学
微泡
化学
前药
催化作用
纳米技术
体内
组合化学
点击化学
材料科学
生物化学
生物
基因
小RNA
生物技术
作者
María Sancho‐Albero,Belén Rubio‐Ruíz,Ana M. Pérez‐López,Víctor Sebastián,Pilar Martín‐Duque,Manuel Arruebo,Jesús Santamarı́a,Asier Unciti‐Broceta
出处
期刊:Nature Catalysis
[Springer Nature]
日期:2019-09-09
卷期号:2 (10): 864-872
被引量:247
标识
DOI:10.1038/s41929-019-0333-4
摘要
The transformational impact of bioorthogonal chemistries has inspired new strategies for the in vivo synthesis of bioactive agents through non-natural means. Among these, Pd catalysts have played a prominent role in the growing subfield of bioorthogonal catalysis by producing xenobiotics and uncaging biomolecules in living systems. However, delivering catalysts selectively to specific cell types still lags behind catalyst development. Here, we have developed a bioartificial device comprising cancer-derived exosomes that are loaded with Pd catalysts by a method that enables the controlled assembly of Pd nanosheets directly inside the vesicles. This hybrid system mediates Pd-triggered dealkylation reactions in vitro and inside cells, and displays preferential tropism for their progenitor cells. The use of Trojan exosomes to deliver abiotic catalysts into designated cancer cells creates the opportunity for a new targeted therapy modality; that is, exosome-directed catalyst prodrug therapy, whose first steps are presented herein with the cell-specific release of the anticancer drug panobinostat. Targeted therapy is an important approach to reduce the side effects of medicinal drugs. This work reports the synthesis of catalytically active Pd nanostructures in exosomes that selectively target cancer cells for drug activation using biorthogonal chemistry.
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