Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s.

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ID: 14391
2015
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Ranked #67 of 112 articles by views in Journal of the American Chemical Society

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Abstract
The efficient delivery of bioactive compounds into cells is a major challenge in drug discovery. We report herein the development of novel methods for intracellular delivery of functional proteins (including antibodies) and native small-molecule drugs by making use of cell-penetrating poly(disulfide)s (CPDs). CPDs were recently shown to be rapidly taken up by mammalian cells in endocytosis-independent pathways, but their applications for delivery of proteins and native small-molecule drugs have not been demonstrated. With our newly developed, CPD-assisted approaches, rapid and "bioorthogonal" loading of cargos was carried out with pre-synthesized CPDs, in two steps and in a matter of minutes under aqueous conditions. The resulting CPD-cargo conjugates were used immediately for subsequent cell delivery studies. With the versatility and flexibility of these methods, we further showed that they could be used for immediate delivery of a variety of functional cargos with minimum chemical and genetic manipulations. The minimal cell cytotoxicity of these CPDs and their cargo-loaded conjugates further highlights the unique advantage of this new cell-transduction method over other existing strategies and ensures that our entire delivery protocol is compatible with subsequent live-cell experiments and biological studies.
Reference Key
fu2015intracellularjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Fu, Jiaqi;Yu, Changmin;Li, Lin;Yao, Shao Q;
Journal Journal of the American Chemical Society
Year 2015
DOI
10.1021/jacs.5b08130
URL
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