Lectin-gated and glycan functionalized mesoporous silica nanocontainers for targeting cancer cells overexpressing Lewis X antigen

Abstract

Gated mesoporous silica nanoparticles can deliver payload upon the application of a predefined stimulus, and therefore are promising drug delivery systems. Despite their important role, relatively low emphasis has been placed on the design of gating systems that actively target carbohydrate tumor cell membrane receptors. We describe herein a new Lewis X (Le) antigen-targeted delivery system comprising mesoporous silica nanoparticles (MSNs) loaded with ATTO 430LS dye, functionalized with a Le derivative (1) and capped with a fucose-specific carbohydrate-binding protein (Aleuria aurantia lectin (AAL)). This design takes advantage of the affinity of AAL for Le overexpressed receptors in certain cancer cells. In the proximity of the cells, AAL is detached from MSNs to bind Le, and selectins in the cells bind Le in the gated MSNs, thereby inducing cargo delivery. Gated MSNs are nontoxic to colon cancer DLD-1 cells, and ATTO 430LS dye delivered correlated with the amount of Le antigen overexpressed at the DLD-1 cell surface. This is one of the few examples of MSNs using biologically relevant glycans for both capping (via interaction with AAL) and targeting (via interaction with overexpressed Le at the cell membrane).

Mesoporous Silica Nanoparticles for Drug Delivery

“…The dysregulation of certain enzymes and/or specific antibodies, both hypo-or overexpression, in certain pathological states or diseased tissues can also be used for triggering the therapeutic cargo release from MSNs. [93], [94], [95], [96], [97], [98], [99], [100], [101], [102] Similarly, the change in redox potential as it happens in tumor tissues where the glutathione concentration can be four times higher than in healthy tissues, can be employed to develop responsive MSNs. [10], [103][104], [105], [106], [107], [108], [109], [110], [111], [112] On the other hand, external stimuli are those than can be activated remotely by the clinician, who is under control at all times.…”

Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities

“…Anti-Selectin antibodies, antibodies that recognize selectin ligands, or other platforms to block Selectin-mediated recognition of their endogenous ligands have been contemplated as a means of blocking cancer metastasis [ 10 , 136 , 137 ]. It is noteworthy that other pharmacological approaches to disrupting Selectin-ligand interactions are also being pursued [ 125 , 138 , 139 , 140 , 141 ].…”

Glycosylated Nanoparticles for Cancer-Targeted Drug Delivery

“…Cancer cells exhibit membranal structure changes via changes in external monosaccharide-related target molecules, such as proteins and lipids, that aid in tumorigenesis, malignant transformation, and tumor dissemination (27). For example, overexpression of sialic acid on the cell surface creates a negative charge on membranes and repulsion between cells, which helps cells enter the bloodstream (28).…”