Purpose The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH₂ as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety. Methods Fe-MIL-101-NH₂ was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction. Magnetic resonance relaxometry and MRI were carried out on phantoms of the MOF system suspended in polymer solution. Drug dissolution studies were conducted using Franz cells. For MOF cytotoxicity, commercially available fibroblasts L929 were cultured in Eagle’s Minimum Essential Medium supplemented with 10% fetal bovine serum. Results MOF particles were loaded with 12% of isoniazid. The particle size (3.37–6.45 μm) depended on the micronization method used. The proposed drug delivery system can also serve as the MRI contrast agent. The drug dissolution showed extended release of isoniazid. MOF particles accumulated in the L929 fibroblast cytoplasmic area, suggesting MOF release the drug inside the cells. The cytotoxicity confirmed safety of MOF system. Conclusions The application of MOF for extended release inhalable system proposes the novel strategy for delivery of standard antimycobacterial agents combined with monitoring of their distribution within the lung tissue.

The theranostic approach to local tuberculosis treatment allows drug delivery and imaging of the lungs for a better control and personalization of antibiotic therapy. Metal-organic framework (MOF) Fe-MIL-101-NH2 nanoparticles were loaded with isoniazid. To optimize their functionality a 2³ factorial design of spray-drying with poly(lactide-co-glycolide) and leucine was employed. Powder aerodynamic properties were assessed using a twin stage impinger based on the dose emitted and the fine particle fraction. Magnetic resonance imaging (MRI) contrast capabilities were tested on porous lung tissue phantom and ex vivo rat lungs. Cell viability and uptake studies were conducted on murine macrophages RAW 246.9. The final product showed good aerodynamic properties, modified drug release, easier uptake by macrophages in relation to raw isoniazid-MOF, and MRI contrast capabilities. Starting from raw MOF, a fully functional inhalable theranostic system with a potential application in personalized tuberculosis pulmonary therapy was developed.

The analysis of the NMR relaxation function for microheterogenous systems usually starts with the decomposition of the relaxation function to discrete components, or finding a continuous distribution of the components. Several approaches can be applied to do this: linear least-squares fitting, non-linear least-squares fitting or inversion of the data, based on the Laplace transformation. The spin-grouping technique - a correlated analysis of the spin-lattice relaxation function (recovery or decay) and spin-spin relaxation decay (free induction decay or Carr-Purcell decay) - usually enables a decomposition of relaxation data into a proper set of discrete components. In our paper, we present CracSpin, a program for one and/or two-dimensional analysis of the relaxation function in the time domain. It uses Marquardt's algorithm for non-linear least-squares fitting. The results of analyses of simulated data containing discrete as well as continuous distributions of the components are shown. CracSpin resolves the components of FID even if the ratio of their relaxation times is as small as 2, for comparable component magnitudes (at least about 10% of total signal) and for signal-to-noise ratio (S/N) >100. If the ratio of component relaxation times is higher than ~3, the decomposition is satisfactory for S/N >10, even for a component magnitude of about 1%. The noise level is defined here as equal to the three standard deviations of the normal distribution. The two-dimensional analysis significantly improves the quality of the multicomponent decomposition, for composed decays or in the case of close values of the relaxation time of the components. The representative examples of the analysis, starting from spin-lattice relaxation curves, as well as from spin-spin relaxation curves, are presented and discussed.

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe₃O₄@SiO₂@Au nanoparticles (NPs) were designed. The encapsulation of Fe₃O₄ cores inside continuous SiO₂ shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T₂ contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe₃O₄@SiO₂@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm⁻²). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10–15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43–50%. This increase of the cytotoxic properties of the Fe₃O₄@SiO₂@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.