Photothermal Hydrogel Composites Featuring G4-Carbon Nanomaterial Networks for Staphylococcus aureus Inhibition.

Microbial infections represent a significant health risk, often leading to severe complications and, in some cases, even fatalities. As a result, there is an urgent need to explore innovative drug delivery systems and alternative therapeutic techniques. The photothermal therapy has emerged as a promising antibacterial approach and is the focus of this study. Herein, we report the successful synthesis of two distinct supramolecular composite hydrogels by incorporating graphene oxide (GO) and single-walled carbon nanotubes (SWNTs) into guanosine quadruplex (G4) based hydrogels containing covalently bound ß-cyclodextrin (ß-CD). The G4 matrix was synthesized through a two-step process, establishing a robust network between G4 and ß-CDs, followed by the encapsulation of either GO or SWNTs. Comprehensive characterization of these composite hydrogels were conducted using analytical techniques, including circular dichroism, Raman spectroscopy, rheological investigations, X-ray diffraction, and scanning electron microscopy. A notable discovery from the conducted research is the differential photothermal responses exhibited by the hydrogels when exposed to near-infrared laser irradiation. Specifically, SWNT-based hydrogels demonstrated superior photothermal performance, achieving a remarkable temperature increase of up to 52 °C, in contrast to GO-based hydrogels, which reached a maximum of 34 °C. These composite hydrogels showed good cytotoxicity evaluation results and displayed synergistic antibacterial activity against Staphylococcus aureus, positioning them as promising candidates for antibacterial photothermic platforms, particularly in the context of wound treatment. This study offers a valuable contribution to the development of advanced and combined therapeutic strategies for combating microbial infections and highlights the potential of carbon nanomaterial-enhanced supramolecular hydrogels in photothermal therapy applications.

3D-Shaped Binders of Unfolded Proteins Inducing Cancer Cell-Specific Endoplasmic Reticulum Stress In Vitro and In Vivo.

The amount of unfolded proteins is increased in cancer cells, leading to endoplasmic reticulum (ER) stress. Therefore, cancer cells are sensitive to drugs capable of further enhancing ER stress. Examples of such drugs include the clinically approved proteosome inhibitors bortezomib and carfilzomib. Unfortunately, the known ER stress inducers exhibit dose-limiting side effects that justify the search for better, more cancer-specific drugs of this type. Herein, we report on FeC 2, which binds to unfolded proteins prevents their further processing, thereby leading to ER stress and ROS increase in cancer cells, but not in normal cells. FeC 2 exhibits low micromolar toxicity toward human acute promyelocytic leukemia HL-60, Burkitt's lymphoma BL-2, T-cell leukemia Jurkat, ovarian carcinoma A2780, lung cancer SK-MES-1, and murine lung cancer LLC1 cells. Due to the cancer-specific mode of action, 2 is not toxic in vivo up to the dose of 147 mg/kg, does not affect normal blood and bone marrow cells at the therapeutically active dose, but strongly suppresses both primary tumor growth (confirmed in Nemeth-Kellner lymphoma and LLC1 lung cancer models of murine tumor) and spreading of metastases (LLC1).

Nucleic Acid Probes in Bio-Imaging and Diagnostics: Recent Advances in ODN-Based Fluorescent and Surface-Enhanced Raman Scattering Nanoparticle and Nanostructured Systems.

Raman nanoparticle probes are a potent class of optical labels for the interrogation of pathological and physiological processes in cells, bioassays, and tissues. Herein, we review the recent advancements in fluorescent and Raman imaging using oligodeoxyribonucleotide (ODN)-based nanoparticles and nanostructures, which show promise as effective tools for live-cell analysis. These nanodevices can be used to investigate a vast number of biological processes occurring at various levels, starting from those involving organelles, cells, tissues, and whole living organisms. ODN-based fluorescent and Raman probes have contributed to the achievement of significant advancements in the comprehension of the role played by specific analytes in pathological processes and have inaugurated new possibilities for diagnosing health conditions. The technological implications that have emerged from the studies herein described could open new avenues for innovative diagnostics aimed at identifying socially relevant diseases like cancer through the utilization of intracellular markers and/or guide surgical procedures based on fluorescent or Raman imaging. Particularly complex probe structures have been developed within the past five years, creating a versatile toolbox for live-cell analysis, with each tool possessing its own strengths and limitations for specific studies. Analyzing the literature reports in the field, we predict that the development of ODN-based fluorescent and Raman probes will continue in the near future, disclosing novel ideas on their application in therapeutic and diagnostic strategies.

Dynameric G-quadruplex-dextran hydrogels for cell growth applications.

Hybrid dextran-G-quartet produces tunable biocompatible three-dimensional thixotropic hydrogels, able to support cell growth.

Solid-Phase Synthesized Copolymers for the Assembly of pH-Sensitive Micelles Suitable for Drug Delivery Applications.

Diblock copolymers of polyhistidine are known for their self-assembly into micelles and their pH-dependent disassembly due to the amphiphilic character of the copolymer and the unsaturated imidazole groups that undergo a hydrophobic-to-hydrophilic transition in an acidic pH. This property has been largely utilized for the design of drug delivery systems that target a tumor environment possessing a slightly lower extracellular pH (6.8-7.2). The main purpose of this study was to investigate the possibility of designed poly(ethylene glycol)-polyhistidine sequences synthesized using solid-phase peptide synthesis (SPPS), to self-assemble into micelles, to assess the ability of the corresponding micelles to be loaded with doxorubicin (DOX), and to investigate the drug release profile at pH values similar to a malignant extracellular environment. The designed and assembled free and DOX-loaded micelles were characterized from a physico-chemical point of view, their cytotoxicity was evaluated on a human breast cancer cell line (MDA-MB-231), while the cellular areas where micelles disassembled and released DOX were assessed using immunofluorescence. We concluded that the utilization of SPPS for the synthesis of the polyhistidine diblock copolymers yielded sequences that behaved similarly to the copolymeric sequences synthesized using ring-opening polymerization, while the advantages of SPPS may offer facile tuning of the histidine site or the attachment of a large variety of functional molecules.

Injectable Thixotropic ß-Cyclodextrin-Functionalized Hydrogels Based on Guanosine Quartet Assembly.

Facile method for the preparation of ß-cyclodextrin-functionalized hydrogels based on guanosine quartet assembly was described. A series of seven hydrogels were prepared by linking ß-cyclodextrin molecules with guanosine moieties in different ratios through benzene-1,4-diboronic acid linker in the presence of potassium hydroxide. The potassium ions acted as a reticulation agent by forming guanosine quartets, leading to the formation of self-sustained transparent hydrogels. The ratios of the ß-cyclodextrin and guanosine components have a significant effect on the internal structuration of the components and, correspondingly, on the mechanical properties of the final gels, offering a tunablity of the system by varying the components ratio. The insights into the hydrogels' structuration were achieved by circular dichroism, scanning electron microscopy, atomic force microscopy, and X-ray diffraction. Rheological measurements revealed self-healing and thixotropic properties of all the investigated samples, which, in combination with available cyclodextrin cavities for active components loading, make them remarkable candidates for specific applications in biomedical and pharmaceutical fields. Moreover, all the prepared samples displayed selective antimicrobial properties against S. aureus in planktonic and biofilm phase, the activity also depending on the guanosine and cyclodextrin ratio within the hydrogel structure.

Monomethine cyanine probes for visualization of cellular RNA by fluorescence microscopy.

We have studied spectral-luminescent properties of the monomethine cyanine dyes both in their free states and in the presence of either double-stranded deoxyribonucleic acids (dsDNAs) or single-stranded ribonucleic acids (RNAs). The dyes possess low fluorescence intensity in an unbound state, which is increased up to 479 times in the presence of the nucleic acids. In the presence of RNAs, the fluorescence intensity increase was stronger than that observed in the presence of dsDNA. Next, we have performed staining of live and fixed cells by all prepared dyes. The dyes proved to be cell and nuclear membrane permeant. They are photostable and brightly stain RNA-containing organelles in both live and fixed cells. The colocalization confirmed the specific nucleoli staining with anti-Ki-67 antibodies. The RNA digestion experiment has confirmed the selectivity of the dyes toward intracellular RNA. Based on the obtained results, we can conclude that the investigated monomethine cyanine dyes are useful fluorescent probes for the visualization of intracellular RNA and RNA-containing organelles such as nucleoli by using fluorescence microscopy.

New 2,9-disubstituted-1,10-phenanthroline derivatives with anticancer activity by selective targeting of telomeric G-quadruplex DNA.

Fifteen new 1,10-phenanthrolines disubstituted at positions 2 and 9 via amide bonds with different heterocycles have been designed and synthesized as G-quadruplex DNA stabilizers. Ten compounds were evaluated for the in vitro anticancer activity against 60 human tumor cell lines panel, four of them showing a very good inhibitory activity on several cell lines. To assess the ability of the most active compounds to interact with G-quadruplex DNA (G4-DNA), circular dichroism experiments were performed. The potency of the compounds to stabilize the G4-DNA has been shown from the thermal denaturation experiments. The mechanism of compounds binding to DNA and to G4-DNA was theoretically investigated by molecular docking studies. The experimental results demonstrated excellent capacity of the two compounds bearing two pyridin-3-yl residues (methylated and non-methylated) to act as selective G-quadruplex binders with promising anticancer activity.

Cyclodextrin Encapsulated pH Sensitive Dyes as Fluorescent Cellular Probes: Self-Aggregation and In Vitro Assessments.

We have designed and synthesized a series of novel, supramolecular, long-lived fluorescent probes based on the host-guest inclusion complexes formation between fluorescent indolizinyl-pyridinium salts and ß-cyclodextrin. Fluorescence and electrospray ionisation mass spectrometry experiments, supported by theoretical molecular docking studies, were utilized in the monitoring of the inclusion complexes formation, evidencing the appearance of corresponding 1:1 and 1:2 species. Additionally, the influence of the guest molecule over the aggregation processes of the cyclodextrin inclusion complexes was investigated by transmission electron microscopy. The absence of cytotoxicity, cellular permeability, long-lived intracellular fluorescence, and in time specific accumulation within acidic organelles identified the investigated supramolecular entities as remarkable candidates for intracellular fluorescence probes. Co-staining experiments using specific organelle markers revealed the fact that, after a 24-h incubation period, the inclusion complexes accumulate predominantly in lysosomes rather than in mitochondria. This study opens new possibilities for a broad range of fluorescent dyes with solubility and high toxicity issues, able to form inclusion complexes with ß-cyclodextrin, to be tested as intracellular fluorescence probes.

Prof. Dr. Gheorghe Bilascu. Pro patria.

Gheorghe Bilascu came to Cluj from Budapest, where he enjoyed all the privileges reserved for the high-class people in the Hungarian capital city, in 1919. He renounced this comfortable existence in order to establish the Romanian Dental Education in Cluj. When he made this choice, he was aware that he would sacrifice his life for a national ideal. The following text describes the background and events that shaped the future of Romanian dentistry in Cluj, driven by the personality of Gheorghe Bilascu.

Mass Spectrometry as a Complementary Approach for Noncovalently Bound Complexes Based on Cyclodextrins.

An important and well-designed solution to overcome some of the problems associated with new drugs is provided by the molecular encapsulation of the drugs in the cyclodextrins (CDs) cavity, yielding corresponding inclusion complexes (ICs). These types of non-covalent complexes are of current interest to the pharmaceutical industry, as they improve the solubility, stability and bioavailability of the guest molecules. This review highlights several methods for cyclodextrin ICs preparation and characterization, focusing mostly on the mass spectrometry (MS) studies that have been used for the detection of noncovalent interactions of CDs inclusion complexes and binding selectivity of guest molecules with CDs. Furthermore, the MS investigations of several ICs of the CD with antifungal, antioxidants or fluorescent dyes are presented in greater details, pointing out the difficulties overcome in the analysis of this type of compounds.

Aqueous Dispersion of Single-Walled Carbon Nanotubes Using Tetra-Phenyl Bimesitylene Derivative via Noncovalent Modification and Improved Antimicrobial Activity.

Tetra-arylbimesityl derivative containing carboxylic groups have successfully been utilized in dispersing single-walled carbon nanotubes (SWNTs) in aqueous solutions through sonication and centrifugation procedures. The dispersion process and the characterization of final stabilized SWNTs were accomplished using analytical techniques, providing sufficient evidences on the preparation of the dispersed SWNTs in water. All the prepared SWNT water dispersions were evaluated for antimicrobial activity against three different reference strains namely Escherichia coli, Staphylococcus aureus and Candida albicans, and have shown considerable selective activity against the Gram-positive strain Staphylococcus aureus.

Gheorghe Bȃrlea MD, PhD, pupil and collaborator of Professor Bilascu.

Being the first collaborator and assistant of Professor Gheorghe Bilascu, the founder of Cluj and National School of Dentistry, Dr. Gheorghe Bârlea kept very close to his master in developing the Dental Medicine in Cluj and in Romania, from 1908 to 1936. From the beginning of his career, he was involved in the establishment of the new Dental Clinic in the University of Superior Dacia as well as in the compilation of the teaching curriculum at the level of the avant-garde universities at that time. He was deeply involved in the recognition of Dentistry as discipline and medical practice and in the official achievement of the law and practice of this profession in Romania. Dr. Bârlea devoted his life and wotk to the cultural and social life of the Romanians, his efforts contributing to the Great Union of Romania. Passing away at an early age, Dr. Bârlea left Romanian dental profession without an important support.

G-Quartet hydrogels for effective cell growth applications.

Functional G-quartet hydrogels formed from natural guanosine cross linked with benzene-1,4-diboronic acid and Mg2+ support cell growth with no visible signs of gel degradation.

Biography of Professor Cornel Tiberiu Opris. Professional maturity.

Professor Cornel Tiberiu Opris was the founder and Chair of the Clinic and University Department of Oral and Maxillofacial Surgery in Cluj, after the Education Reform of 1948. The article illustrates how the founder of these institutions led a valiant struggle for obtaining and arranging a location for the newly established Faculty of Dentistry, within the Institute of Medicine and Pharmacy. Professor Cornel Tiberiu Opris established himself as the most prodigious researcher at the Faculty for over a quarter-century, until his retirement, introducing his original conception in the therapeutic and surgical field. He created in Cluj-Napoca a specialist medical school by imposing national prestige for the institution that he led.

Optimization of Polyplex Formation between DNA Oligonucleotide and Poly(ʟ-Lysine): Experimental Study and Modeling Approach.

The polyplexes formed by nucleic acids and polycations have received a great attention owing to their potential application in gene therapy. In our study, we report experimental results and modeling outcomes regarding the optimization of polyplex formation between the double-stranded DNA (dsDNA) and poly(ʟ-Lysine) (PLL). The quantification of the binding efficiency during polyplex formation was performed by processing of the images captured from the gel electrophoresis assays. The design of experiments (DoE) and response surface methodology (RSM) were employed to investigate the coupling effect of key factors (pH and N/P ratio) affecting the binding efficiency. According to the experimental observations and response surface analysis, the N/P ratio showed a major influence on binding efficiency compared to pH. Model-based optimization calculations along with the experimental confirmation runs unveiled the maximal binding efficiency (99.4%) achieved at pH 5.4 and N/P ratio 125. To support the experimental data and reveal insights of molecular mechanism responsible for the polyplex formation between dsDNA and PLL, molecular dynamics simulations were performed at pH 5.4 and 7.4.

Aspects from the biography of Professor Cornel Tiberiu Opris. The Beginnings.

Professor Cornel Tiberiu Opris was the founder of the clinic for Oral and Maxillofacial Surgery, and also the first to teach this specialty in Cluj-Napoca in the first half of the twentieth century. Earlier in his profession, Dr. Cornel Opris went from research into human physiology to practical activity in the field of surgery, to which he was more attracted. He was active both in research and Oral and Maxillofacial plastic surgery, facing unfavorable material and social conditions, exacerbated by the circumstances of war and the relocation of the Faculty of Medicine to Sibiu. This article presents the life and work of Prof. Dr. Cornel Opris, with particular reference to the stage of education, the problems associated with "family, society and school."

Professor Gheorghe Bilascu's contribution to the development of science and culture in Romania.

When speaking about Professor Gheorghe Bilascu (1863-1926) and his major contribution to the establishment of Romanian medical education in Cluj, he should be considered not only in terms of scientist and creator of the Dental School, but also through his commitment to the development of science and culture in Romania. A wealthy dentist in Budapest where he graduated from the Dental School, he supported a lot of Romanian students to attend schools and universities in the Budapest, thus contributing to the development of culture in his own country. Finally, he left his private practice in the Capital of Hungary to come to Cluj to support the efforts of building the Dental School and profession in Romania. This paper illustrates the contribution that Professor Gheorghe Bilascu made to the development of higher education in Romania, as well as his support of the local culture.

Supramolecular rulers enabling selective detection of pure short ssDNA via chiral self-assembly.

Multivalent self-assembly of trifunctional aromatic propellers and ssDNA results in the formation of chiral supramolecular assemblies that can be used for the detection of small fragments of ssDNA with different lengths and compositions.