Molecular recognition and proteoglycan mimic arrangement: modulating cisplatin toxicity.

We have demonstrated that cisplatin (CP), an anticancer drug, showed a preference for binding the sulfated-L-iduronic acid (S-L-IdoA) unit over the sulfated-D-glucuronic acid unit of heparan sulfate. The multivalency of S-L-IdoA, such as in the proteoglycan mimic, resulted in distinct modes of cell-surface engineering in normal and cancer cells, with these disparities having a significant impact on CP-mediated toxicity.

Synergestic interplay of uronic acid and sulfation composition of heparan sulfate on molecular recognition to activity.

Heparan sulfate (HS) is ubiquitous polysaccharide on the surface of all mammalian cells and extracellular matrices. The incredible structural complexity of HS arises from its sulfation patterns and disaccharide compositions, which orchestrate a wide range of biological activities. Researchers have developed elegant synthetic methods to obtain well-defined HS oligosaccharides to understand the structure-activity relationship. These studies revealed that specific sulfation codes and uronic acid variants could synergistically modulate HS-protein interactions (HSPI). Additionally, the conformational flexibility of l-Iduronic acid, a uronic acid unit has emerged as a critical factor in fine-tuning the microenvironment to modulate HSPI. This review delineates how uronic acid composition in HS modulates protein binding affinity, selectivity, and biological activity. Finally, the significance of sulfated homo-oligo uronic acid as heparin mimics in drug development is also discussed.

Fluorescent glyco-gold nanocluster induced EGFR mediated targeting of cancer cells.

A lot of attention has been focused on the functionalization of carbohydrate ligands on specific sizes and shapes of gold nanoparticles (AuNPs), where ultrasmall fluorescent AuNPs have not been well explored for direct imaging. Herein, we have engineered fluorescent gold nanoclusters with sulfated oligo-iduronic acid ligands (I34), which strongly bind to the HB-EGF receptor over FGF2, and regulate EGF receptor-mediated cancer cell homing in both two- and three-dimensional (2D and 3D) cell culture systems. These results offer a new practical and direct imaging tool for carbohydrate research.

Pairing Nanoparticles Geometry with TLR Agonists to Modulate Immune Responses for Vaccine Development.

Nanotechnology-based vaccine development necessitates understanding the crucial biophysical properties of nanostructures that alter immune responses. In this study, we demonstrate the synergistic effect of gold nanoparticles (AuNPs) shapes with toll-like receptor (TLR) agonists in immune modulation activity. Our results showed that CpG- and imidazoquinoline-conjugated rod-shaped AuNPs display relatively fast uptake by bone marrow-derived macrophage cells but exhibit poor immunogenic responses compared to their spherical and star-shaped AuNP counterparts. Surprisingly, star-shaped AuNPs exhibited intense pro-inflammatory cytokine secretion. Further mechanistic studies showed that star-shaped AuNPs were abundantly localized in the late endosome and lysosomal regions, whereas rod-shaped AuNPs were majorly sequestered in the mitochondrial region. These findings reveal that the shape of the nanostructures plays a pivotal role in driving the adjuvant molecules toward their receptors and altering immune responses.