Hyperphosphatemia is a typical complication of end-stage renal disease, characterized by elevated and life-threatening serum phosphate levels. Hemodialysis does not enable sufficient clearance of phosphate, due to slow cell-to-plasma kinetics of phosphate ions; moreover, dietary restrictions and conventional treatment with oral phosphate binders have low success rates, together with adverse effects. Here, we developed a new concept of phosphate-trapping liposomes, to improve and prolong the control over serum phosphate levels. We designed liposomes modified with polyethylene glycol and encapsulated with the phosphate binder ferric citrate (FC liposomes). These liposomes were found to trap phosphate ions in their inner core, and thereby lower free phosphate ion concentrations in solution and in serum. The FC liposomes showed higher phosphate binding ability as phosphate concentrations increased. Moreover, these liposomes showed a time-dependent increase in uptake of phosphate, up to 25 h in serum. Thus, our findings demonstrate effective long-term phosphate trapping by FC liposomes, indicating their potential to reduce serum phosphate toxicity and improve current management of hyperphosphatemia.

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.

BackgroundProgress has been achieved with the introduction of biologics for the management of inflammatory/autoimmune diseases such as rheumatoid arthritis (RA), however such medications induce immune suppression, which is nonselective to the pathogenesis of the disease, resulting in higher rates of infections. Therefore, there are unmet medical needs in the treatment of such diseases, which should be addressed by novel approaches. Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the establishment, maintenance and modulation of autoimmune processes.ObjectivesIn the current study, we hypothesized that isolation of circulating autologous tissue-specific homing EVs from RA patients - may improve the delivery of current FDA-approved anti-inflammatory drugs, which will be encapsulated into these EVs. The drug-loaded EVs will be injected back to the diseased subjects and will naturally find their way to the inflamed tissue.ResultsIndeed, we found that autologous labeled EVs, expressing joint/synovia-specific homing receptors (e.g. αVβ3 integrin), derived from blood of diseased arthritic mice (Collagen antibody-induced arthritis model), can migrate toward the inflamed synovia, usingin vivoimaging system (IVIS). Moreover, we show that these EVs strongly expresses glucose transporter 1 (mGLUT1) which in turn, improve their therapeutic potential to be loaded with anti-inflammatory drugs using glucose-coated gold nanoparticles (GNPs). Finally, we show that EVs derived from plasma of RA patients overexpresses αVβ3 integrin and taken up by LPS/TNFα-induced activated human synovial cell linein vitro.ConclusionOverall, we show the potential of autologous circulating EVs of RA patients to serves as natural nano-carrier for current FDA-approved drugs. We believe that this strategy will increase the specificity and efficiency of current treatment, therefore it will reduce side effects and will improve the quality of life of RA patients and potentially other autoimmune disease patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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