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

ABSTRACT

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.

KEY WORDS

bioconjugation click chemistry CuAAC drug delivery nanostructure 

ABBREVIATIONS

AAC

azide-alkyne cycloaddition

AgNP

silver nanoparticle

AIBN

azobisisobutyronitrile

Alk

alkyne

ATRP

atom transfer radical polymerization

AuNP

gold nanoparticle

Az

azide

BNP

bionanoparticle

BPDS

bathophenanthroline disulphonated disodium salt

CD

cyclodextrin

CMC

critical micelle concentration

CNT

carbon nanotube

CPMV

cowpea mosaic virus

CTA

chain transfer agent

CuAAC

Cu(I)-catalyzed azide-alkyne cycloaddition

DBU

1,8-diazabicyclo[5.4.0]undec-7-ene

DDS

drug delivery system

DIPEA

N,N-diisopropylethylamine

DOTA

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

DOX

doxorubicin

EGF

epidermal growth factor

EGFP

enhanced green fluorescent protein

EPL

expressed protein ligation

EPR

enhanced permeability and retention

FA

folic acid

FPLC

fast protein liquid chromatography

FR

folate receptor

FRET

fluorescence resonance energy transfer

GFP

green fluorescent protein

HABA

2-(4-hydroxyphenylazo)benzoic acid

HEMA

2-hydroxyethyl methacrylate

LA

lactic acid

LbL

layer-by-layer

MAA

methacrylic acid

MBP

maltose binding protein

MNP

magnetic nanoparticle

MRI

magnetic resonance imaging

MWCNT

multi-walled carbon nanotube

NHS

N-hydroxysuccinimide

NP

nanoparticle

PAA

poly(acrylic acid)

PACA

poly(alkyl cyanocrylate)

PBD

poly(butadiene)

PCL

poly(ε-caprolactone)

PCN

polymer-caged nanobin

PDMA

poly(N,N-dimethylacrylamide)

PEG

poly(ethylene glycol)

PEI

poly(ethylene imine)

PEO

poly(ethylene oxide)

PET

position emission tomography

PGA

poly-L-glutamic acid

PIC

polyion complex

PLL

poly-L-lysine

PMA

poly(methacrylate)

PMDETA

N,N,N′,N′,N″-pentamethyldiethylenetriamine

PMPC

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

PNIPAM

poly (N-isopropylacrylamide)

PrMA

propyl methacrylate

PS

poly(styrene)

PTMCC

poly(2-methyl-2-carboxytrimethylene carbonate)

PtNP

platinum nanoparticle

PTQY

photoluminescence quantum yield

PVP

poly(vinyl pyrrolidone)

QD

quantum dot

RAFT

reversible addition-fragmentation chain transfer

RGD

Arg-Gly-Asp

ROS

reactive oxygen species

SiNP

silica nanoparticle

SPAAC

strain-promoted azide-alkyne cycloaddition

SPION

superparamagnetic iron oxide nanoparticle

STEM

scanning transmission electron microscopy

SWCNT

single-walled carbon nanotube

TBTA

tris(benzyltriazolylmethyl)amine

TCEP

tris(carboxyethyl)phosphine

TEC

thiol-ene coupling

THPTA

tris(hydroxypropyltriazolylmethyl)amine

TMS

trimethylsilyl

VNP

viral nanoparticle

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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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