Arany nanorészecskéket tartalmazó bioaktív üveg – biopolimér kompozítok előállítása, jellemzése és alkalmazhatósága: Synthesis, characterization and applicability of bioactive glass – biopolymer composites with gold nanoparticles

Considering that the median age of our population is increasing, bone disorders or skin regeneration problems are of significant concern. The bioactive glass-biopolymer composites are materials with real potential to be used in tissue engineering. It is well-known, that the bioactive glasses (BG) can lead the promotion of growth of granulation tissue. The gold nanoparticles (AuNPs; ~20 nm) can induced the acceleration of wound healing including tissue regeneration, connective tissue regeneration and angiogenesis. It was demonstrated that the AuNPs in the sol-gel derived glass structure retain their properties. Alginate-pullulan (Alg-Pll) composites have good bioactivity and in vivo qualities in terms of bone regeneration. The goal of this study was to obtain the functional composites for future tissue engineering applications using BG with AuNPs introduced in Alg-Pll composites. After structural and morphological characterization of the composites, in vitro and in vivo bioactivity and biocompatibility were evaluated. The obtained results suggest that the obtained composites are materials for future soft tissue and bone engineering applications.  Kivonat A várható élettartam növekedésével egyre növekszik azon betegek száma, amelyek ortopédiai vagy bőr rekonstrukcióra szorulnak. A bioaktív üveg-biopolimer kompozitok potenciálisan alkalmazható anyagok a szövettani sebészetben. Ismert dolog, hogy a bioaktív üvegek (BG) elősegítik a granulációs szövetek növekedését. Az arany nanorészecskék (AuNPs; ~20 nm) gyorsítják a sebgyógyulást beleértve angiogenézist, a szövetek és kötőszövet regenerálódását. Tudjuk, hogy a szól-gél módszerrel előállított üveg szerkezetben bevitt AuNPs képes megőrizni ezen tulajdonságait. Az alginát-pullulán (kompozitok) remek bioaktivitásuknak köszönhetően aktívan részt vesznek az in vivo csont regenerálódásban. A tanulmány célja, hogy olyan funkcionális kompozitokat hozzunk létre, amelyek alkalmazhatók a szövettani sebészetben. Ehhez az Alg-Pll kompozitokban AuNPs tartalmazó BG vittünk be, majd szerkezeti és morfológiai jellemzéseket végeztünk. Ezt követtően az in vitro és in vivo bioaktivitás, valamint biokompatibilitást vizsgáltuk. A kapott eredmények azt sugallják, hogy az előállított kompozitok megfelelnek a lágyrész- és csonttechnikai alkalmazás elvárásainak

Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer

Background: Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. Methods: Next-generation sequencing of the whole miRNome and SERS profiling were performed on urine samples collected from 15 patients with BC and 16 control subjects (CTRLs). A retrospective cohort (BC = 66 and CTRL = 50) and RT-qPCR were used to confirm the selected differently expressed miRNAs. Diagnostic accuracy was assessed using machine learning algorithms (logistic regression, naive Bayes, and random forest), which were trained to discriminate between BC and CTRL, using as input either miRNAs, SERS, or both. The molecular stratification of BC based on miRNA and SERS profiling was performed to discriminate between high-grade and low-grade tumors and between luminal and basal types. Results: Combining SERS data with three differentially expressed miRNAs (miR-34a-5p, miR-205-3p, miR-210-3p) yielded an Area Under the Curve (AUC) of 0.92 +/- 0.06 in discriminating between BC and CTRL, an accuracy which was superior either to miRNAs (AUC = 0.84 +/- 0.03) or SERS data (AUC = 0.84 +/- 0.05) individually. When evaluating the classification accuracy for luminal and basal BC, the combination of miRNAs and SERS profiling averaged an AUC of 0.95 +/- 0.03 across the three machine learning algorithms, again better than miRNA (AUC = 0.89 +/- 0.04) or SERS (AUC = 0.92 +/- 0.05) individually, although SERS alone performed better in terms of classification accuracy. Conclusion: miRNA profiling synergizes with SERS profiling for point-of-care diagnostic and molecular stratification of BC. By combining the two liquid biopsy methods, a clinically relevant tool that can aid BC patients is envisaged

Combination therapy of simvastatin and 5, 6-dimethylxanthenone-4-acetic acid synergistically suppresses the aggressiveness of B16.F10 melanoma cells.

The major drawback of current anti-angiogenic therapies is drug resistance, mainly caused by overexpression of the transcription factor, hypoxia-inducible factor 1α (HIF-1α) as a result of treatment-induced hypoxia, which stimulates cancer cells to develop aggressive and immunosuppressive phenotypes. Moreover, the cancer cell resistance to anti-angiogenic therapies is deeply mediated by the communication between tumor cells and tumor-associated macrophages (TAMs)-the most important microenvironmental cells for the coordination of all supportive processes in tumor development. Thus, simultaneous targeting of TAMs and cancer cells could improve the outcome of the anti-angiogenic therapies. Since our previous studies proved that simvastatin (SIM) exerts strong antiproliferative actions on B16.F10 murine melanoma cells via reduction of TAMs-mediated oxidative stress and inhibition of intratumor production of HIF-1α, we investigated whether the antitumor efficacy of the anti-angiogenic agent-5,6-dimethylxanthenone-4-acetic acid (DMXAA) could be improved by its co-administration with the lipophilic statin. Our results provide confirmatory evidence for the ability of the combined treatment to suppress the aggressive phenotype of the B16.F10 melanoma cells co-cultured with TAMs under hypoxia-mimicking conditions in vitro. Thus, proliferation and migration capacity of the melanoma cells were strongly decelerated after the co-administration of SIM and DMXAA. Moreover, our data suggested that the anti-oxidant action of the combined treatment, as a result of melanogenesis stimulation, might be the principal cause for the simultaneous suppression of key molecules involved in melanoma cell aggressiveness, present in melanoma cells (HIF-1α) as well as in TAMs (arginase-1). Finally, the concomitant suppression of these proteins might have contributed to a very strong inhibition of the angiogenic capacity of the cell co-culture microenvironment

Designing Theranostic Agents Based on Pluronic Stabilized Gold Nanoaggregates Loaded with Methylene Blue for Multimodal Cell Imaging and Enhanced Photodynamic Therapy

At present, multifunctional noble metal-based nanocomposites are extensively investigated for their potential in performing cellular imaging, diagnostics, and therapy by integration of unique plasmonic properties with the spectroscopic expression and therapeutic activity of appropriate drug. In this work, we report the fabrication of 3-dimensional (3-D) close-packed nanoassemblies of gold nanoparticles by controlling the aggregation of individual nanoparticles in solution and subsequent stabilization of formed aggregates by Pluronic block copolymer (F127) coating. Besides conferring high stability, Pluronic mediates the loading of Methylene Blue (MB) molecules which exhibit interesting spectroscopic and photochemical properties to be employed as both optical label and photosensitizing drug. Indeed, here we demonstrate the pertinence of the fabricated nanoassemblies to provide optical imaging of murine colon carcinoma cells (C-26) via both Raman and fluorescence signals collected from MB molecules, specifically by using scanning confocal surface-enhanced resonant raman spectroscopy (SERRS) and fluorescence lifetime imaging microscopy (FLIM) techniques. The specific configuration of as fabricated nanoassemblies allows a small population of MB molecules to be located in very small areas between the aggregated nanoparticles (“hot spots”) to provide SERRS signal while the other population remains captured in Pluronic coating and preserves both its fluorescence signal and singlet-oxygen generation capability. Remarkably, we demonstrate an enhanced photodynamic therapeutic activity of MB-loaded gold nanoaggregates against murine colon carcinoma cells (C-26), as compared to the free photosensitizer. To our knowledge, this is the first report on plasmonic nanoplatforms conveying photosensitizing drug into cells to operate as optical label via both SER­(R)S and FLIM and to perform enhanced photodynamic therapy