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The growing number of acute drug abuse overdoses demands the development of innovative detoxification strategies for emergency purposes. In this study, an innovative approach for the application of porous Zr-based metal–organic frameworks for the treatment of acute overdoses of popular drugs of abuse including amphetamine, methamphetamine, cocaine, and MDMA is presented. A comprehensive approach determining the efficacy and the kinetics of drug removal, considering dosage, adsorption time, and adsorption mechanisms, was tested and corroborated with density functional theory (DFT) modeling. The experimental results showed high removal efficiency reaching up to 90% in the case of the application of the NU-1000 metal–organic framework. The difference Raman spectroscopy method presented in this study corroborated with DFT-based vibrational analysis allows the detection of drug adsorbed in the MOF framework even with as low a concentration as 5 mg/g. Additionally, the drug adsorption mechanisms were modeled with DFT, showing the π–π stacking in a vast majority of considered cases. The performance and influence on the living organisms were evaluated throughout the in vitroand in vivoexperiments, indicating that Zr-based MOFs could serve as efficient, organic, safe drug adsorbents.

In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal–organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000) ACF loadings. The drug release profiles from prepared composites showed different release kinetics depending on the local pore environment. The long-term ACF release with the effective antiviral ACF concentration was observed for all studied ACF@MOF composites. The density functional theory (DFT) calculations allowed us to determine that π–π stacking together with electrostatic interaction plays an important role in acriflavine adsorption and release from ACF@MOF composites. The molecular docking results have shown that acriflavine interacts with several possible binding sites within the RBD and binding site at the RBD/ACE2 interface. The cytotoxicity and ecotoxicity results have confirmed that the prepared ACF@MOF composites may be considered potentially safe for living organisms. The complementary experimental and theoretical results presented in this study have confirmed that the ACF@MOF composites may be considered a potential candidate for the COVID-19 treatment, which makes them good candidates for clinical trials.

The removal of uremic toxins from patients with acute kidney injury is a key issue in improving the quality of life for people requiring peritoneal dialysis. The currently utilized method for the removal of uremic toxins from the human organism is hemodialysis, performed on semipermeable membranes where the uremic toxins, along with small molecules, are separated from proteins and blood cells. In this study, we describe a mixed-linker modulated synthesis of zirconium-based metal–organic frameworks for efficient removal of uremic toxins. We determined that the efficient adsorption of uremic toxins is achieved by optimizing the ratio between −amino functionalization of the UiO-66 structure with 75% of −NH2groups within organic linker structure. The maximum adsorption of hippuric acid and 3-indoloacetic acid was achieved by UiO-66-NH2(75%) and by UiO-66-NH2(75%) 12.5% HCl prepared by modulated synthesis. Furthermore, UiO-66-NH2(75%) almost completely adsorbs 3-indoloacetic acid bound to bovine serum albumin, which was used as a model protein to which uremic toxins bind in the human body. The high adsorption capacity was confirmed in recyclability test, which showed almost 80% removal of 3-indoloacetic acid after the third adsorption cycle. Furthermore, in vitrocytotoxicity tests as well as hemolytic activity assay have proven that the UiO-66-based materials can be considered as potentially safe for hemodialytic purposes in living organisms.

In this study, we present a modulated synthesis nanocrystalline defective UiO-66 metal–organic framework as a potential chloroquine diphosphate (CQ) delivery system. Increasing the concentration of hydrochloric acid during the modulated synthesis resulted in a considerable increase of pore volume, which enhanced the CQ loading in CQ@UiO-66 composites. Drug release tests for CQ@UiO-66 composites have confirmed prolonged CQ release in comparison with pure CQ. In vivo tests on a Danio reiromodel organism have revealed that CQ released from CQ@UiO-66 25% showed lower toxicity and fewer cardiotoxic effects manifested by cardiac malformations and arrhythmia in comparison to analogous doses of CQ. Cytotoxicity tests proved that the CQ loaded on the defective UiO-66 cargo resulted in increased viability of cardiac cells (H9C2) as compared to incubation with pure CQ. The experimental results presented here may be a step forward in the context of reducing the cardiotoxicity CQ.