Cyclodextrin-based metal-organic frameworks as nano platforms for biomedical applications

Cyclodextrins (CDs) form a family of naturally abundant, inexpensive, cyclic oligosaccharides, consisting of truncated cone-shaped molecules, with a hydrophobic internal cavity and a hydrophilic external surface. Through the coordination of CDs with alkali metal ions (Na+, Rb+, Cs+, K+,…) biocompatible, carbohydrate CD-based, porous metal-organic frameworks (CD-MOFs) can be obtained. These CD-MOFs are attractive materials for practical applications as they can be considered as biocompatible, biodegradable, inexpensive, and sustainable nanoporous MOF alternatives. Hence, CD-MOFs have already been found in a wide range of applications, such as molecular adsorption, separation and recognition, drug delivery, as host template for nanoparticle synthesis, and light emission and sensing. In this work, we first designed macro- and nanosized core, as well as core-shell, γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) and used them as platforms for the encapsulation of dye molecules to develop the first CD-MOF-based ratiometric optical thermometer materials. A novel dye combination was employed for this purpose, i.e., the duo rhodamine B (RhB) and fluorescein (FL). RhB is highly temperature-sensitive, whereas FL is less temperature-sensitive, and its luminescence emission peak is used as a reference. Promising results in terms of thermometric properties were obtained for a whole series of dye-encapsulated γ-CD-MOF materials based on this dye combination, with high relative sensitivities, even up to 5%K-1, for the dye-encapsulated 75%RhB-25%FL nanosized γ-CD-MOF, among the highest performance values reported so far for luminescent dual thermometers. In our study, we have additionally developed a simple yet effective preparation method for core−shell γ-CD MOFs, allowing effective manipulation of the γ-CD-MOF shell growth. The proposed method allows incorporation of the FL and RhB dyes in the γ-CD-MOFs in a more controlled manner, enhancing the efficiency of the developed ratiometric (macro) γ-CD-MOF thermometers. In recent years, the incorporation of metal or metal oxide nanoparticles (NPs) into porous MOFs to form NP-MOF structures has attracted great interest. Although procedures for the deposition of Ag and/or Au NPs (AgNPs, AuNPs) in MOFs have already been reported, their application with CD-MOFs has not been investigated thoroughly yet. Both AgNPs and AuNPs are plasmonic, which means they could be exploited to concentrate light at a certain wavelength, providing local heating and, thus, be employed for photothermal therapy and can play a beneficial role when it comes to CD-MOFs used as drug delivery systems, as local heating can speed up the drug release. In this work, we additionally investigated different routes of depositing AuNPs and AgNPs in a quick and easy manner into nanosized CD-MOFs. The loading of the nanoparticles can be easily steered by increasing or decreasing the amount of used metal precursors. The nanoparticles can be synthesized at low temperatures which do not affect the structure nor crystallinity of the nano CD-MOFs. It was also shown that small and very uniform AuNPs and AgNPs can be obtained upon dissolving the CD-MOF template. Therefore, this is also a route to yield well water-dispersible metal nanoparticles without the use of any ligands or surfactants. Analogously to the first employed dye combination of RhB and FL, the thermometry properties of the nano CD-MOFs with deposited AuNPs and AgNPs were obtained upon embedding a mixture of a different dye combination, i.e. the RhB and rhodamine 110 (Rh110) pair in the pores of the CD-MOFs. This is the first work where CD-MOFs are proposed for the development of luminescent thermometric materials, and in combination with plasmonic AuNPs and AgNPs. By employing this approach, various fluorescent dyes can be combined, which opens new possibilities toward the future development of a wide range of ratiometric biological (plasmonic) nanothermometers