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

Journal of the American Chemical Society
Jiaqi FuShao Q Yao

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...Continue Reading

References

Jul 12, 2001·The Journal of Biological Chemistry·O ZelphatiJ Corbeil
Mar 30, 2002·Advanced Drug Delivery Reviews·William L Jorgensen, Erin M Duffy
Sep 27, 2002·Current Opinion in Pharmacology·Mark A Lindsay
Nov 2, 2002·The Journal of Biological Chemistry·Jean Philippe RichardBernard Lebleu
Dec 12, 2002·Chemical Reviews·Jean-Bernard Denault, Guy S Salvesen
Oct 22, 2005·Chemical Society Reviews·Kostas Kostarelos, Andrew D Miller
Apr 25, 2006·Nature Chemical Biology·Sunil ShaunakSteve Brocchini
Aug 31, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gisela TünnemannM Cristina Cardoso
Nov 16, 2006·Journal of the American Chemical Society·Igor SlowingVictor S-Y Lin
Feb 27, 2007·ACS Chemical Biology·Stephen M Fuchs, Ronald T Raines
Feb 23, 2008·Organic & Biomolecular Chemistry·Su Ling NgShao Q Yao
Dec 5, 2008·Chemical Reviews·Meredith A Mintzer, Eric E Simanek
Mar 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Brian R McNaughtonDavid R Liu
Mar 25, 2009·British Journal of Pharmacology·Frederic HeitzGilles Divita
Sep 19, 2009·Journal of Biomolecular Screening·John T NortonSui Huang
Apr 24, 2010·Nature Reviews. Immunology·Louis M WeinerShangzi Wang
Aug 31, 2010·Journal of the American Chemical Society·Yan-Li ZhaoJeffrey I Zink
Nov 26, 2010·MAbs·Andrea L J MarschallStefan Dübel
Dec 24, 2010·Cell Communication and Signaling : CCS·Ganta Vijay ChaitanyaPhanithi Prakash Babu
Apr 15, 2011·Current Opinion in Biotechnology·Arjen van den Berg, Steven F Dowdy
Jun 2, 2011·Accounts of Chemical Research·Neal K Devaraj, Ralph Weissleder
Dec 2, 2011·Accounts of Chemical Research·Sejin SonWon Jong Kim
Jan 3, 2012·Methods in Enzymology·Robert P LyonPeter D Senter
Jan 5, 2012·Chemical Society Reviews·Zongxi LiJeffrey I Zink
Jan 21, 2012·Trends in Biotechnology·Adrian G Torres, Michael J Gait
Mar 21, 2012·Accounts of Chemical Research·Juliane Nguyen, Francis C Szoka
Sep 22, 2012·Bioconjugate Chemistry·Hanieh KhaliliSteve Brocchini
Oct 6, 2012·Advanced Drug Delivery Reviews·Theresa M Allen, Pieter R Cullis
Dec 12, 2012·Accounts of Chemical Research·Carmen CollFélix Sancenón
Jan 3, 2013·The Journal of Pharmacy and Pharmacology·Oktay TacarCrispin R Dass
Feb 1, 2013·Journal of the American Chemical Society·Eun-Kyoung BangStefan Matile
Feb 7, 2013·Pharmacological Reviews·Hywel D WilliamsChristopher J H Porter
Apr 17, 2013·Scientific Reports·Kristopher MontroseGeoffrey W Krissansen
Apr 17, 2014·Journal of the American Chemical Society·Giulio GaspariniStefan Matile
May 6, 2014·Bioconjugate Chemistry·George BadescuAntony Godwin
Aug 19, 2014·Bioconjugate Chemistry·Ailing FuVincent M Rotello
Sep 23, 2014·Angewandte Chemie·Quentin MichaudelPhil S Baran
Oct 9, 2014·Angewandte Chemie·Tianmeng SunYounan Xia
Dec 6, 2014·Nature Communications·Dong Hoon HanMin Jae Lee

❮ Previous
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Citations

Dec 5, 2015·ACS Applied Materials & Interfaces·Shi-Ying LiXian-Zheng Zhang
Aug 30, 2016·Journal of the American Chemical Society·Nicolas ChuardStefan Matile
Sep 16, 2016·ACS Applied Materials & Interfaces·Ning ZhangMingming Ma
May 4, 2017·ACS Nano·Berta Esteban-Fernández de ÁvilaJoseph Wang
Nov 22, 2016·Advanced Healthcare Materials·Christopher T TurnerNicolas H Voelcker
Jul 26, 2017·Journal of the American Chemical Society·Emmanuel DeriveryMarcos Gonzalez-Gaitan
Mar 15, 2018·Organic & Biomolecular Chemistry·Mao LiCarsten Schmuck
Jan 4, 2017·Chemical Science·Kristina M HamillYitzhak Tor
Oct 13, 2015·Chemical Communications : Chem Comm·Giulio Gasparini, Stefan Matile
Dec 14, 2018·Journal of Biomaterials Science. Polymer Edition·Jilan WangChengkun Qin
Nov 22, 2018·Biomaterials Science·Sussana A ElkassihDaniel J Siegwart
Nov 30, 2019·Soft Matter·Raju BejSuhrit Ghosh
Feb 27, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ya-Ping XiaoXiao-Qi Yu
Jun 6, 2020·Biomaterials Science·Song Zhang, Yiyun Cheng
May 20, 2020·Chembiochem : a European Journal of Chemical Biology·Raju BejSuhrit Ghosh
Aug 29, 2020·Chemical Communications : Chem Comm·Si Si LiewShao Q Yao
Sep 10, 2019·Advanced Materials·Xiaofei QinWei Huang
Sep 28, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Tuanwei LiuXinlin Yang
Apr 21, 2018·Chemical Science·Nicolas ChuardStefan Matile
Feb 19, 2019·Chemical Science·Yiyang LinMolly M Stevens
Aug 17, 2020·Organic & Biomolecular Chemistry·Georg M ScheutzBrent S Sumerlin
Apr 11, 2018·Nature Communications·Zhenjing ZhangYiyun Cheng
Aug 25, 2020·Beilstein Journal of Organic Chemistry·Rémi MartinentStefan Matile
Aug 21, 2020·Nature Communications·Anthonius H J Engwerda, Stephen P Fletcher
Nov 10, 2020·Protein Science : a Publication of the Protein Society·Francesca AnsonJeanne A Hardy
Dec 3, 2020·American Journal of Physiology. Cell Physiology·Jan Gettemans, Brian De Dobbelaer
Feb 17, 2021·Biomacromolecules·Francesca AnsonS Thayumanavan

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