the two main synthetic strategies that were used to construct perfectly branched
dendrimers: the divergent and the convergent approaches [10]. Over time, accelerated
alternatives have been developed in order to increase the synthetic efficiency and to
reach a substantially higher number of peripheral functionalities. Furthermore, clever
adaptations and combination of expeditious strategies based on suitably functionalized
cores or dendrons have allowed the direct access of complex dendritic structures. The
perfect control of tri-dimensional parameters (size, shape, geometry); the covalent
introduction of functionalities to the core, branches, or high number of surface groups;
or the physical encapsulation of functionalities in the microenvironment created by
cavities can all help confer optimal properties of solubility and hydrophilic/hydrophobic
balance for the required application. Thus, creativity has allowed these structures to
become integrated with nearly all contemporary scientific disciplines.
Undoubtedly, the merging of biology and nanomedicine represents new fields that
have generated the highest passion for these architectures. Thus, the very unique structures
and properties of glycodendrimers have motivated their use in numerous disciplines
including nanomedicine, with biomedical and therapeutic applications such as drug or
gene delivery devices with beneficial EPR effect for anticancer therapy [15, 16], and
antibacterial, antiviral, or antitumor agents. The use of dendrimers in biological systems,
together with systematic studies of the most common dendritic scaffolds to determine
their biocompatibility, including in vitro and in vivo cytotoxicity, biostability, and
immunogenicity, have been extensively reviewed [17, 18]. One typical example concerns
the use of dendrimers as “glycocarriers” for the control of multimeric presentation of
biologically relevant carbohydrate moieties, which are useful for targeting modified tissue
in malignant diseases for diagnostic and therapeutic purposes. In such molecules
(glycodendrimers), the saccharide portions are conjugated according to the principles of
dendritic growth or are ligated to pre-existing highly functionalized and repetitive
dendritic scaffolds having varied molecular weights and structures. Since they first
appeared in the literature in 1993 [19], glycodendrimers and related glycodendrons,
with their spheroidal or dendritic wedge structures, have been designed as bioisosteres
of cell surface multi-antennary glycans and have stimulated wide interest within the
scientific community. Similarly to conventional dendritic structures, glycodendrimers can
be obtained as dendrons, as spherical or globular architectures, or as “hybrid dendronizedpolymers” according to divergent, convergent, or accelerated approaches. All these
original synthetic clusters were constructed in such a way that their number of surface
groups, shapes, and carbohydrate contents could be varied at will with a controlled
integration of dendritic building blocks. As artificial glycoforms, the elaborated
glycodendritic architectures are classically used to study, rationalize, and understand the
critical carbohydrate–protein interactions that are reinforced when multivalent ligand
copies are presented to clustered biological receptors through the well-known “glycoside
cluster effect” [20, 21]. As such, they notably constituted powerful synthetic tools for the
development of potent bacterial or viral inhibitors together with efficient inhibitors of
mammalian lectins such as galectines, which are involved in cancer progression.
Although the applications of glycoclusters and related glycodendrimers as potent
biological process inhibitors or effectors have been extensively reviewed [22–31], the
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
301
dendrimers: the divergent and the convergent approaches [10]. Over time, accelerated
alternatives have been developed in order to increase the synthetic efficiency and to
reach a substantially higher number of peripheral functionalities. Furthermore, clever
adaptations and combination of expeditious strategies based on suitably functionalized
cores or dendrons have allowed the direct access of complex dendritic structures. The
perfect control of tri-dimensional parameters (size, shape, geometry); the covalent
introduction of functionalities to the core, branches, or high number of surface groups;
or the physical encapsulation of functionalities in the microenvironment created by
cavities can all help confer optimal properties of solubility and hydrophilic/hydrophobic
balance for the required application. Thus, creativity has allowed these structures to
become integrated with nearly all contemporary scientific disciplines.
Undoubtedly, the merging of biology and nanomedicine represents new fields that
have generated the highest passion for these architectures. Thus, the very unique structures
and properties of glycodendrimers have motivated their use in numerous disciplines
including nanomedicine, with biomedical and therapeutic applications such as drug or
gene delivery devices with beneficial EPR effect for anticancer therapy [15, 16], and
antibacterial, antiviral, or antitumor agents. The use of dendrimers in biological systems,
together with systematic studies of the most common dendritic scaffolds to determine
their biocompatibility, including in vitro and in vivo cytotoxicity, biostability, and
immunogenicity, have been extensively reviewed [17, 18]. One typical example concerns
the use of dendrimers as “glycocarriers” for the control of multimeric presentation of
biologically relevant carbohydrate moieties, which are useful for targeting modified tissue
in malignant diseases for diagnostic and therapeutic purposes. In such molecules
(glycodendrimers), the saccharide portions are conjugated according to the principles of
dendritic growth or are ligated to pre-existing highly functionalized and repetitive
dendritic scaffolds having varied molecular weights and structures. Since they first
appeared in the literature in 1993 [19], glycodendrimers and related glycodendrons,
with their spheroidal or dendritic wedge structures, have been designed as bioisosteres
of cell surface multi-antennary glycans and have stimulated wide interest within the
scientific community. Similarly to conventional dendritic structures, glycodendrimers can
be obtained as dendrons, as spherical or globular architectures, or as “hybrid dendronizedpolymers” according to divergent, convergent, or accelerated approaches. All these
original synthetic clusters were constructed in such a way that their number of surface
groups, shapes, and carbohydrate contents could be varied at will with a controlled
integration of dendritic building blocks. As artificial glycoforms, the elaborated
glycodendritic architectures are classically used to study, rationalize, and understand the
critical carbohydrate–protein interactions that are reinforced when multivalent ligand
copies are presented to clustered biological receptors through the well-known “glycoside
cluster effect” [20, 21]. As such, they notably constituted powerful synthetic tools for the
development of potent bacterial or viral inhibitors together with efficient inhibitors of
mammalian lectins such as galectines, which are involved in cancer progression.
Although the applications of glycoclusters and related glycodendrimers as potent
biological process inhibitors or effectors have been extensively reviewed [22–31], the
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
301