Accordingly, in an early report, hybrid NPs 37 have been synthesized by combining
the Tn and Lewis oligosaccharides tumor markers (33 and 34), a peptide from
tetanus toxoid (TT) as T-cell helper (35 or 36), and an inert glucose moiety 32 to
control the density of the above conjugates (Fig. 10). Preliminary data showed that
gold GNPs 37 exhibited potent immunogenic activity. In a very recent work, Barchi
Jr. and coworkers reported another potential tumor vaccine construction prepared
from gold NPs [83]. Gold GNPs (45–50) have been loaded with three components
that included: (a) glycopeptides 38–42 consisting of Mucin-4-based peptides with
the Thomsen–Friedenreich antigen (TF) at various positions, (b) a 28-residue
peptide from complement-derived protein C3d as a B-cell activating molecular
adjuvant 43, and (c) an inert linker 44 (in Fig. 10, the linker portion is highlighted
for glycopeptides and adjutant peptide). In vivo studies on sera from mice
immunized with GNPs showed small but statistically significant antibody responses
(both IgG and IgM) against the carbohydrate antigen. In addition to TFfunctionalized gold GNPs (46–49), glycoconstructs from the peptides without the
TF-antigen 45 or linker alone 50 also showed some immunogenicity. Among the
TF-functionalized gold GNPs, the mono-functionalized conjugates (46, 47, and 49)
showed the highest activity of the GNPs with two TF units (48).
The respective positioning of the TF antigen along the peptide chain, as in GNPs
49 with the antigen at the 10th position, showed better selectivity toward IgG over
IgM, whereas conjugates with the sugar at other positions (46 and 47) exhibited
similar selectivity for both IgG and IgM. Even though the results are still preliminary, the efficiency of the NPs to acts as scaffolds for vaccine construction was
shown successfully in the above applications.
Fig. 10 Molecular structures of the gold NP-based tumor vaccine constructs
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
317
the Tn and Lewis oligosaccharides tumor markers (33 and 34), a peptide from
tetanus toxoid (TT) as T-cell helper (35 or 36), and an inert glucose moiety 32 to
control the density of the above conjugates (Fig. 10). Preliminary data showed that
gold GNPs 37 exhibited potent immunogenic activity. In a very recent work, Barchi
Jr. and coworkers reported another potential tumor vaccine construction prepared
from gold NPs [83]. Gold GNPs (45–50) have been loaded with three components
that included: (a) glycopeptides 38–42 consisting of Mucin-4-based peptides with
the Thomsen–Friedenreich antigen (TF) at various positions, (b) a 28-residue
peptide from complement-derived protein C3d as a B-cell activating molecular
adjuvant 43, and (c) an inert linker 44 (in Fig. 10, the linker portion is highlighted
for glycopeptides and adjutant peptide). In vivo studies on sera from mice
immunized with GNPs showed small but statistically significant antibody responses
(both IgG and IgM) against the carbohydrate antigen. In addition to TFfunctionalized gold GNPs (46–49), glycoconstructs from the peptides without the
TF-antigen 45 or linker alone 50 also showed some immunogenicity. Among the
TF-functionalized gold GNPs, the mono-functionalized conjugates (46, 47, and 49)
showed the highest activity of the GNPs with two TF units (48).
The respective positioning of the TF antigen along the peptide chain, as in GNPs
49 with the antigen at the 10th position, showed better selectivity toward IgG over
IgM, whereas conjugates with the sugar at other positions (46 and 47) exhibited
similar selectivity for both IgG and IgM. Even though the results are still preliminary, the efficiency of the NPs to acts as scaffolds for vaccine construction was
shown successfully in the above applications.
Fig. 10 Molecular structures of the gold NP-based tumor vaccine constructs
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
317