Intracellular Delivery of Functional Proteins and Native Drugs by Cell-Penetrating Poly(disulfide)s.
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.
Department of Chemistry, National University of Singapore , 117543 Singapore.
Jiaqi
J
Fu
Department of Chemistry, National University of Singapore , 117543 Singapore.
Changmin
C
Yu
Department of Chemistry, National University of Singapore , 117543 Singapore.|Key Laboratory of Flexible Electronics and Institute of Advanced Materials, National Jiangsu Synergistic Innovation Center for Advanced Materials, Nanjing Tech University , Nanjing 211816, P. R. China.
Lin
L
Li
Department of Chemistry, National University of Singapore , 117543 Singapore.
Shao Q
SQ
Yao
D040761:Biomimetic Materials / Q000737:chemistry*; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D057846:Cell-Penetrating Peptides; D004220:Disulfides; D004337:Drug Carriers; D011506:Proteins