Noble Metals Nanoparticles Capped with Thiolated Amphiphilic Cyclodextrins: toward a Novel Multifunctional Hybrid Assembly

Over the past decade, nanoassemblies based on amphiphilic cyclodextrin (ACyDs) have been proposed as suitable molecule carriers with high potential in numerous biomedical applications. ACyDs have been obtained by covalent grafting of hydrophobic group (alkylthio chain) and hydrophilic group (polyethylene glycol chain -PEG-) on the narrow and the wide rim of CD cavity, respectively. Furthermore, the presence of various terminal groups can address both the capability of ACyD to interact with cellular membrane (-NH2 for attractive, -OH repulsive, sugar for specific interactions), and to complex different guests, such as anticancer, antiviral, nutraceutical drugs, as well photosensitisers for photoactivated therapy or DNA for gene delivery. Multifunctionality have been achieved by combining self-assembled ACyD and combined doses of metal and/or phototherapeutics for dual action. With this idea in mind, here we report an unprecedented thiolated ACyD (SC16SH), with one -SH ending on one of the PEG chains able to form a covalent shell on gold/silver nano-cores, starting from the commercial ?-cyclodextrin, through a multi step synthesis. The thiolation of the PEG in SC16OH precursor has been realized by the preliminary introduction of an iodine on one terminus. The structure of new compounds has been determined on the basis of NMR studies (1H-NMR, 13C-NMR, gHSQCAD) and MALDI-TOF MS analyses. Gold and silver nanoparticles (AuNPs and AgNPs) were synthesized by chemical reduction of the metal precursors by citric acid and NaBH4 respectively. The hybrid metal/ACyD nanoconstructs were fromed in aqueous solution by assembly of metal NPs with different doses of ACyD and characterized by UV-Vis and TEM. Interestingly, in the presence of SC16SH in addition to the typical plasmonic absorption band of AuNPs centered at 530 nm, a red-shifted band centered at around 670 nm can be detectable. This band can be attributed to the formation of larger metal constructs. The morphology of the hybrid assembly, investigated by TEM characterization, reveals the presence of 20-30 nm AuNPs covered by a cyclodextrin layer which probably imparts high stability to the solution within several days. Also AgNPs were covered by SC16SH, displaying a more pronounced tendency to the interparticle aggregation. Altogether, these assemblies can be promising as multifunctional systems in biological applications, such as for photothermal treatments of cancer cells or into the fabrication of more complex bioconjugates for intracellular delivery of drugs.