Gold nanoparticles decorated by clustered multivalent cone-glycocalixarenes actively improve the targeting efficiency toward cancer cells

Abstract

A novel approach for multivalent targeting by using gold nanoparticles noncovalently decorated by tight functionalization with a cone-glycocalixarene bearing four mannose units is reported. The targeting efficiency of these multivalent nanoparticles is shown to be remarkably improved compared to that of nanoparticles bearing a monovalent mannosylated derivative.

Multivalent and Multifunctional Calixarenes in Bionanotechnology

“…This feature allowed us to insert glycocalixarenes with proper geometry and sugar epitopes in liposome double layers [70] or on the surface of gold nanoparticles. [71] In the first case, a 1,3-alternate calix [4]arene spanning the thickness of the phospholipid bilayer and exposing glucoside units provided the liposome with the ability of interacting with glucose binding Concanavalin A used a model of cell membrane receptor. In a second case, we noncovalently functionalised the surface of AuNPs coated with dodecanthiol chains with cone calixarenes bearing α-mannoside units at the upper rim and propyl chains at the lower rim.…”

“…Compared to other multivalent scaffolds, calixarenes offer the possibility to shape the size, the valency and the stereochemical disposition in the space of the multiple ligating units. Moreover, the introduction of proper aliphatic chains and the presence itself of the lipophilic aromatic external walls of the macrocycle ensure the possibility to tune the amphiphilic character of the multivalent ligand [115] so that they can be noncovalently included in the lipophilic monolayers of nanoparticles [71] and nanocapsules [116] or in the double layers of liposomes [70,117] to address specific biological targets. Playing with this palette of instruments, organic chemists might design proper systems, based on calixarenes, able to interact with proteins, nucleic acids or even biomacromolecules present on the surface of cells/bacteria/viruses.…”

Mannose‐Functionalized Nanoscaffolds for Targeted Delivery in Biomedical Applications

“…Since monomannose‐modified nanosystems have exhibited relatively lower affinity to target proteins or cells, it has been assumed that the receptor binding capacity of conjugates is highly dependent upon the multivalency effect of targeting units towards MR, thereby resulting in significant anticancer and antibacterial activity. To realize multivalent grafting of mannose, different chemical modification methods have been exploited but were limited by labor‐intensive work and costs.…”

Nanotechnology in Glycomics: Applications in Diagnostics, Therapy, Imaging, and Separation Processes

“…Good examples are synthetic polymers, such as poly(acrylamidophenyl‐α‐mannose‐ co ‐acrylamide) attached to AuNPs, layer‐by‐layer modifications of MNPs coated with polysaccharide shells of hyaluronan and chitosan . These polymers were applied for the selective enrichment of glycoconjugates in more complex biological samples and for the non‐covalent modification of hydrophobic, dodecanethiol‐stabilized AuNPs (synthesized by Brust—Schiffrin method) by multivalent glycocalixarenes with four mannose units to improve targeting efficiency toward intact cells . Glycan parts of different enzymes frequently serve as models to study interactions with lectins.…”