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GATG Dendrimers and PEGylated Block Copolymers: from Synthesis to Bioapplications

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Abstract

Dendrimers are synthetic macromolecules composed of repetitive layers of branching units that emerge from a central core. They are characterized by a tunable size and precise number of peripheral groups which determine their physicochemical properties and function. Their high multivalency, functional surface, and globular architecture with diameters in the nanometer scale makes them ideal candidates for a wide range of applications. Gallic acid-triethylene glycol (GATG) dendrimers have attracted our attention as a promising platform in the biomedical field because of their high tunability and versatility. The presence of terminal azides in GATG dendrimers and poly(ethylene glycol) (PEG)-dendritic block copolymers allows their efficient functionalization with a variety of ligands of biomedical relevance including anionic and cationic groups, carbohydrates, peptides, or imaging agents. The resulting functionalized dendrimers have found application in drug and gene delivery, as antiviral agents and for the treatment of neurodegenerative diseases, in diagnosis and as tools to study multivalent carbohydrate recognition and dendrimer dynamics. Herein, we present an account on the preparation and recent applications of GATG dendrimers in these fields.

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Abbreviations

AMCA:

Aminomethylcoumarin

CA:

HIV capsid protein

CTD:

C-Terminal domain

Con A:

Concanavalin A

CuAAC:

Cu(I)-catalyzed azide-alkyne cycloaddition

DTPA:

Diethylenetriaminepentaacetate

DOTA:

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

DO3A:

Tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate

EGFP:

Enhanced green fluorescent protein

FDA:

Food and Drug Administration

FITC:

Fluorescein isothiocyanate

GATG:

Gallic acid-triethylene glycol

G n :

Dendrimer generation, n denotes the generation number

Glc:

Glucose

HEK293T:

Human embryonic kidney cell line 293T

HIV:

Human immunodeficiency virus

HPMA:

N-(2-hydroxypropyl)methacrylamide

HSV:

Herpes simplex virus

ITC:

Isothermal titration calorimetry

Man:

Mannose

Mor:

Morpholine

MRI:

Magnetic resonance imaging

NOE:

Nuclear Overhauser effect

PAMAM:

Polyamidoamine

PEG:

Poly(ethylene glycol)

PPI:

Polypropylene imine

PIC:

Polyion complex

RGD:

Arginylglycylaspartic acid

SPR:

Surface plasmon resonance

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Acknowledgments

The authors wish to acknowledge past and present lab members who have contributed to the development of dendrimers in our group. This work was financially supported by the Spanish Government (CTQ2009-10963, CTQ2012-34790, CTQ2009-14146-C02-02, CTQ2012-33436) and the Xunta de Galicia (10CSA209021PR and CN2011/037).

Conflict of Interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Organic Chemistry and Center for Research in Biological Chemistry and Molecular Materials (CIQUS), University of Santiago de Compostela, Jenaro de la Fuente s/n, 15782, Santiago de Compostela, Spain

    Ana Sousa-Herves, Ramon Novoa-Carballal, Ricardo Riguera & Eduardo Fernandez-Megia

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  1. Ana Sousa-Herves
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  2. Ramon Novoa-Carballal
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  3. Ricardo Riguera
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  4. Eduardo Fernandez-Megia
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Correspondence to Eduardo Fernandez-Megia.

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Ana Sousa-Herves and Ramon Novoa-Carballal contributed equally to this work.

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Sousa-Herves, A., Novoa-Carballal, R., Riguera, R. et al. GATG Dendrimers and PEGylated Block Copolymers: from Synthesis to Bioapplications. AAPS J 16, 948–961 (2014). https://doi.org/10.1208/s12248-014-9642-3

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