Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
2 Glycodendrimers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
3 Glycofullerenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
4 Glyconanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
5 Gold Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
6 Quantum Dots and Quantum Rods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
7 Iron-Oxide-Based Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
8 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
9 Micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
10 Glycopolymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
11 Nanogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
12 Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
13 Miscellaneous Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
14 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
1 Introduction
Nanoparticles (NPs) conjugated with sugar moieties (referred to here as glyconanoparticles or GNPs) have been extensively used for multivalent presentation of
carbohydrates in biomedical applications. The globular shapes and diversified nanometer sizes of NPs, some of which are comparable to those of biomacromolecules, make
them efficient scaffolds for the syntheses of “glycocalyx-like” building blocks exposing
multiple copies of oligosaccharide conjugates. By using simple and efficient preparative
methods available for the synthesis and functionalization of NPs, a wide variety of
biorelevant glycans have been coated onto the NPs. Furthermore, several molecules
have been attached to single nanoparticle surfaces to afford hybrid NPs and, by varying
the ratios of different ligands, their presentation density can be controlled [1]. A wide
variety of linkers have been used for the chemical ligation between the two partners and
for better exposure of carbohydrate head groups to their cognate molecular receptors,
which is key to achieving high avidity multicontact binding.
By altering experimental conditions, it is possible to tune the dimensions of the
NPs, which is directly coupled to their stability, cytotoxicity and electronic, optical,
and magnetic properties. The size and shape of NPs have been shown to play several
crucial roles in their in vivo characteristics. For instance, renal clearance, liver and
mononuclear phagocyte uptake, and intracellular delivery are a few examples wherein
the use of NPs could be advantageous. Intracellular delivery is also dictated by the
charge of the NP surface groups, and internalization can occur through interaction
with specialized cellular receptors or by one of the endocytosis mechanisms.
In addition, surface functionalization is also a major factor in determining the stability,
toxicity, and long-term circulation abilities of the NPs. Poly(ethyleneglycol) (PEG)
and carbohydrates (including mono- and polysaccharides) are often used to reduce the
toxicity and to achieve the long-term circulation of NPs in the blood stream.
298
N. Kottari et al.
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
2 Glycodendrimers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
3 Glycofullerenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
4 Glyconanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
5 Gold Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
6 Quantum Dots and Quantum Rods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
7 Iron-Oxide-Based Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
8 Liposomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
9 Micelles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
10 Glycopolymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
11 Nanogels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
12 Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
13 Miscellaneous Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
14 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
1 Introduction
Nanoparticles (NPs) conjugated with sugar moieties (referred to here as glyconanoparticles or GNPs) have been extensively used for multivalent presentation of
carbohydrates in biomedical applications. The globular shapes and diversified nanometer sizes of NPs, some of which are comparable to those of biomacromolecules, make
them efficient scaffolds for the syntheses of “glycocalyx-like” building blocks exposing
multiple copies of oligosaccharide conjugates. By using simple and efficient preparative
methods available for the synthesis and functionalization of NPs, a wide variety of
biorelevant glycans have been coated onto the NPs. Furthermore, several molecules
have been attached to single nanoparticle surfaces to afford hybrid NPs and, by varying
the ratios of different ligands, their presentation density can be controlled [1]. A wide
variety of linkers have been used for the chemical ligation between the two partners and
for better exposure of carbohydrate head groups to their cognate molecular receptors,
which is key to achieving high avidity multicontact binding.
By altering experimental conditions, it is possible to tune the dimensions of the
NPs, which is directly coupled to their stability, cytotoxicity and electronic, optical,
and magnetic properties. The size and shape of NPs have been shown to play several
crucial roles in their in vivo characteristics. For instance, renal clearance, liver and
mononuclear phagocyte uptake, and intracellular delivery are a few examples wherein
the use of NPs could be advantageous. Intracellular delivery is also dictated by the
charge of the NP surface groups, and internalization can occur through interaction
with specialized cellular receptors or by one of the endocytosis mechanisms.
In addition, surface functionalization is also a major factor in determining the stability,
toxicity, and long-term circulation abilities of the NPs. Poly(ethyleneglycol) (PEG)
and carbohydrates (including mono- and polysaccharides) are often used to reduce the
toxicity and to achieve the long-term circulation of NPs in the blood stream.
298
N. Kottari et al.