Pharmaceutical Research

, Volume 29, Issue 1, pp 1–34 | Cite as

Click Chemistry for Drug Delivery Nanosystems

  • Enrique Lallana
  • Ana Sousa-Herves
  • Francisco Fernandez-Trillo
  • Ricardo Riguera
  • Eduardo Fernandez-Megia
Expert Review


The purpose of this Expert Review is to discuss the impact of click chemistry in nanosized drug delivery systems. Since the introduction of the click concept by Sharpless and coworkers in 2001, numerous examples of click reactions have been reported for the preparation and functionalization of polymeric micelles and nanoparticles, liposomes and polymersomes, capsules, microspheres, metal and silica nanoparticles, carbon nanotubes and fullerenes, or bionanoparticles. Among these click processes, Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has attracted most attention based on its high orthogonality, reliability, and experimental simplicity for non-specialists. A renewed interest in the use of efficient classical transformations has been also observed (e.g., thiol-ene coupling, Michael addition, Diels-Alder). Special emphasis is also devoted to critically discuss the click concept, as well as practical aspects of application of CuAAC to ensure efficient and harmless bioconjugation.


bioconjugation click chemistry CuAAC drug delivery nanostructure 



azide-alkyne cycloaddition


silver nanoparticle






atom transfer radical polymerization


gold nanoparticle






bathophenanthroline disulphonated disodium salt




critical micelle concentration


carbon nanotube


cowpea mosaic virus


chain transfer agent


Cu(I)-catalyzed azide-alkyne cycloaddition




drug delivery system




1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid




epidermal growth factor


enhanced green fluorescent protein


expressed protein ligation


enhanced permeability and retention


folic acid


fast protein liquid chromatography


folate receptor


fluorescence resonance energy transfer


green fluorescent protein


2-(4-hydroxyphenylazo)benzoic acid


2-hydroxyethyl methacrylate


lactic acid




methacrylic acid


maltose binding protein


magnetic nanoparticle


magnetic resonance imaging


multi-walled carbon nanotube






poly(acrylic acid)


poly(alkyl cyanocrylate)






polymer-caged nanobin




poly(ethylene glycol)


poly(ethylene imine)


poly(ethylene oxide)


position emission tomography


poly-L-glutamic acid


polyion complex








poly(2-methyl-2-carboxyl-propylene carbonate)


poly (N-isopropylacrylamide)


propyl methacrylate




poly(2-methyl-2-carboxytrimethylene carbonate)


platinum nanoparticle


photoluminescence quantum yield


poly(vinyl pyrrolidone)


quantum dot


reversible addition-fragmentation chain transfer




reactive oxygen species


silica nanoparticle


strain-promoted azide-alkyne cycloaddition


superparamagnetic iron oxide nanoparticle


scanning transmission electron microscopy


single-walled carbon nanotube






thiol-ene coupling






viral nanoparticle



This work was financially supported by the Spanish Ministry of Science and Innovation (CTQ2009-10963 and CTQ2009-14146-C02-02) and the Xunta de Galicia (10CSA209021PR).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Enrique Lallana
    • 1
  • Ana Sousa-Herves
    • 1
  • Francisco Fernandez-Trillo
    • 1
  • Ricardo Riguera
    • 1
  • Eduardo Fernandez-Megia
    • 1
  1. 1.Department of Organic Chemistry, Center for Research in Biological Chemistry & Molecular Materials (CIQUS)University of Santiago de CompostelaSantiago de CompostelaSpain

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