hydrophobicity, three-dimensionality, and electronic properties have made them
extremely promising nanostructures with interesting features at the interface of material sciences [50] with biological and medicinal chemistry [51–53]. Interestingly,
initial investigations indicated that these novel and fascinating architectures were
not carcinogenic when applied on skin and did not affect the proliferation and viability
of cells when they were internalized. Hence, despite the observed dose-dependent
toxicity of some derivatives, early observations suggested great promise for
applications in DNA cleavage, photodynamic therapy, and enzymatic inhibition, and
for their antiviral, antibacterial, and antiapoptotic activity [53, 54]. However, the total
absence of solubility in aqueous or physiological media hampered their quick and
efficient development as suitable carriers. The natural repulsion of fullerenes for water
was cleverly circumvented by the application of several methodologies comprising
their entrapment into tailored microcapsules, their suspension with the help of cosolvents, and their chemical derivatization, including their introduction onto peripheral solubilizing appendages. Furthermore, it has been shown that the multivalent
presentation of polar groups around the fullerene spheres could avoid clustering
phenomenon in reasonably dilute solutions and consequently increase the
hydrosolubility of the resulting conjugates. In this context, a variety of chemical
functionalities have been utilized both to increase the hydrophilicity (e.g., OH,
COOH, NH 2 , quaternary ammonium, cyclodextrin groups) and to prepare original
compounds possessing biological and pharmacological activity.
Among the panel of fullerene derivatives proposed through the years, the family
of fulleroglyco-conjugates (also called glycofullerenes) includes promising
candidates that combine crucial properties related to water solubility with biological
relevance. Their emergence particularly arose from the spherical topology of
fullerenes that furnished suitable scaffolds for multivalent presentation of peripheral
carbohydrate residues, and from the development of adapted chemistry for their
efficient and controlled conjugation.
Besides numerous applications validating the beneficial glycoside cluster effect for
lectin recognition and inhibition that have been treated elsewhere [22, 55],
investigations on multivalent enzyme inhibition with globular glycofullerenes have
recently emerged. Most of the enzymes possess a single and deep active site that is
usually less accessible than the shallow CRDs present on multimeric lectins. These
unfavorable structural features first dissuaded the syntheses of multivalent inhibitors.
Additionally, limited success for enzyme inhibition remained disappointing [56, 57].
Nevertheless, two striking examples based on potent fullerene-based glycosylated
structures presenting T h -symmetrical octahedral patterns were recently presented.
The attachment of iminosugar analogues such as 1-deoxynojirimycin, known as
glycosidase inhibitors, around the fullerene framework has been described [58]. In the
context of carbohydrate-processing enzyme inhibition, biological assays involving a
series of glycosidases were used to determine the inhibition profile of polytopic
fullerene 13 decorated with twelve peripheral N-alkyl analogues of 1-deoxynojirimycin (Fig. 5). The presence of the elongated epitopes located at the extremity of the
hexyl spacer and the general poor selectivity of this class of compounds made them
attractive as models for the examination of the influence of multivalency on inhibition
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
307
extremely promising nanostructures with interesting features at the interface of material sciences [50] with biological and medicinal chemistry [51–53]. Interestingly,
initial investigations indicated that these novel and fascinating architectures were
not carcinogenic when applied on skin and did not affect the proliferation and viability
of cells when they were internalized. Hence, despite the observed dose-dependent
toxicity of some derivatives, early observations suggested great promise for
applications in DNA cleavage, photodynamic therapy, and enzymatic inhibition, and
for their antiviral, antibacterial, and antiapoptotic activity [53, 54]. However, the total
absence of solubility in aqueous or physiological media hampered their quick and
efficient development as suitable carriers. The natural repulsion of fullerenes for water
was cleverly circumvented by the application of several methodologies comprising
their entrapment into tailored microcapsules, their suspension with the help of cosolvents, and their chemical derivatization, including their introduction onto peripheral solubilizing appendages. Furthermore, it has been shown that the multivalent
presentation of polar groups around the fullerene spheres could avoid clustering
phenomenon in reasonably dilute solutions and consequently increase the
hydrosolubility of the resulting conjugates. In this context, a variety of chemical
functionalities have been utilized both to increase the hydrophilicity (e.g., OH,
COOH, NH 2 , quaternary ammonium, cyclodextrin groups) and to prepare original
compounds possessing biological and pharmacological activity.
Among the panel of fullerene derivatives proposed through the years, the family
of fulleroglyco-conjugates (also called glycofullerenes) includes promising
candidates that combine crucial properties related to water solubility with biological
relevance. Their emergence particularly arose from the spherical topology of
fullerenes that furnished suitable scaffolds for multivalent presentation of peripheral
carbohydrate residues, and from the development of adapted chemistry for their
efficient and controlled conjugation.
Besides numerous applications validating the beneficial glycoside cluster effect for
lectin recognition and inhibition that have been treated elsewhere [22, 55],
investigations on multivalent enzyme inhibition with globular glycofullerenes have
recently emerged. Most of the enzymes possess a single and deep active site that is
usually less accessible than the shallow CRDs present on multimeric lectins. These
unfavorable structural features first dissuaded the syntheses of multivalent inhibitors.
Additionally, limited success for enzyme inhibition remained disappointing [56, 57].
Nevertheless, two striking examples based on potent fullerene-based glycosylated
structures presenting T h -symmetrical octahedral patterns were recently presented.
The attachment of iminosugar analogues such as 1-deoxynojirimycin, known as
glycosidase inhibitors, around the fullerene framework has been described [58]. In the
context of carbohydrate-processing enzyme inhibition, biological assays involving a
series of glycosidases were used to determine the inhibition profile of polytopic
fullerene 13 decorated with twelve peripheral N-alkyl analogues of 1-deoxynojirimycin (Fig. 5). The presence of the elongated epitopes located at the extremity of the
hexyl spacer and the general poor selectivity of this class of compounds made them
attractive as models for the examination of the influence of multivalency on inhibition
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
307