Thioguanine or 6-thioguanine (6-TG) is major FDA-approved anti-cancer drug, which features limited bioavailability and short plasma half-life time due to quick metabolization. For efficient and prolonged local targeted drug delivery, 6-TG needs to be encapsulated onto a suitable non-toxic sorbent. Metal-Organic Frameworks (MOFs) are promising nanostructured advanced functional materials for encapsulation of small-molecule medicinal drugs by adsorption and the subsequent controlled drug delivery. It is important to learn about molecular level detail of chemical bonds between biologically active small molecule drugs and major structural units in MOFs as drug delivery platform. We report mechanistic studies of encapsulation of 6-TG by adsorption on non-toxic microporous aluminum-containing MOF Basolite A100. We performed a detailed characterization of chemical bonds and the stoichiometry of adsorption complex MOF:Drug by the complementary methods of spectroscopic analysis. Finally, we studied kinetics of controlled release of 6-TG from its MOF-encapsulated form to bodily fluids with different pH at 37 °C. Adsorption of 6-TG from non-toxic FDA-approved solvent dimethylsulfoxide (DMSO) yields an adsorption complex with Basolite A100 MOF. To learn about molecular state of 6-TG in complex with Basolite A100, we have utilized, for the first time, the front face 3-dimensional fluorescence emission spectroscopy at 25 °C. Fluorescence spectra of pure Basolite A100 MOF show optical emission in the near-UV and visible range at λ<sub>exc</sub>&gt;360 nm due to benzenedicarboxylic acid (BDC) linker in the MOF. Upon encapsulation of 6-TG by adsorption on Basolite A100, the fluorescence spectra of Basolite A100 undergo quenching of fluorescence due to formation of complex between the BDC linker and 6-TG molecule. Findings by fluorescence spectroscopy were complemented by near-UV-Visible and Near InfraRed Diffuse Reflectance Spectra and attenuated reflectance FTIR (ATR-FTIR) spectroscopy. Release of MOF-encapsulated 6-TG drug to simulated intestinal fluid (SIF) was studied by in-situ photoluminescence spectroscopy in suspension, and it proceeds on &gt;24 h. time scale. Non-toxic microporous MOF Basolite A100 is a promising novel drug-encapsulation platform for synthesis of new biologically active composite materials and targeted delivery of anti-cancer drugs and similar small molecule nitrogen and sulfur heterocyclic compounds.

Encapsulation of thioguanine anti-cancer drug by adsorption on microporous MOF Basolite A100 and its controlled release

255th National Meeting (2018)

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