The development of innovative nanomaterials for antimicrobial applications has become increasingly important in the context of rising multidrug-resistant (MDR) infections. Silver nanoparticles (AgNPs) are potent antimicrobial agents due to their unique physicochemical properties and broad-spectrum bactericidal activity. However, the synthesis of ultra-small and monodisperse AgNPs with controlled size, shape, and stability remains a significant challenge. In this study, we present a novel reactive nanoemulsion approach that leverages the dual functionality of formamide as both an emulsifying solvent and a reducing agent, allowing rapid in situ reduction of Ag+ to Ag0 and the formation of AgNPs ranging from 2.5 to 8.0 nm (mean 4.8 +/- 1.0 nm) with low polydispersity. The Ac-Dex polymer network ensured particle stability and enabled co-encapsulation of doxycycline (DOX), producing a dual antimicrobial formulation (Ac-Dex-Ag-DOX NPs). These nanoparticles showed minimal cytotoxicity against MCF-7 cells and exhibited strong antibacterial activity against E. coli, with a minimal inhibitory concentration of 3.0 mu g mL-1 (calculated based on Ag concentration). The resultant hybrid material constitutes a hierarchical nano-in-nano architecture, a class of hybrid nanomaterials in which a primary functional nanoparticle (ultra-small AgNPs) is nested within a secondary nanoscale carrier (Ac-Dex NPs). This organization confers multilevel stabilization, precise size control, and dual antimicrobial functionality. The unprecedented combination of reactive nanoemulsion synthesis and polymer-mediated stabilization holds great potential for developing next-generation antimicrobial nanomaterials.

Dendrimers and supramolecular chemistry continue to fascinate researchers due to the endless unrevealed potential of their combination. This study investigates the self-assembly process of a series of hydrophobic triazolylferrocenyl dendrimers in aqueous medium. Deep investigation through NMR spectroscopy, absorption UV-vis spectroscopy along with theoretical simulations demonstrates that the ferrocenyl moieties interact intramolecularly and intermolecularly driving the self-assembly process. Data obtained by DLS, NTA, SEM, TEM, and EF-TEM demonstrate that these dendrimers, in water, spontaneously self-assemble through a hierarchical process. The dendrimers first self-assemble into uniform nanovesicles, which in turn self-assemble into larger vesosomes. The resulting vesosomes emit green non-traditional intrinsic fluorescence, which is a property that emerged from the self-assembled architectures. The vesosomes are efficiently uptaken by cancer cells and induce significant cytotoxic activity against the cancer cell line MCF-7, up to the submicromolar concentration. Positive dendritic effects are identified in the fluorescence intensity and in the cytotoxic activity of the vesosomes, which follow the trend G0-9Fc < G1-27Fc < G2-81Fc. This work showcases the remarkable potential of combining the two dynamic fields of dendrimers and supramolecular chemistry, which resulted in green fluorescent vesosomes capable of performing the dual role of cell imaging and killing, with potential applications in nanotheranostics.

Nitric oxide (NO) and ursodeoxycholic acid (UDCA) are endogenous molecules involved in physiological processes associated with inflammation. Since inflammatory processes are present in the mechanisms of many diseases, these molecules are important for the development of new drugs. Herein, we describe the synthesis of a well-defined bifunctional dendrimer with 108 termini bearing 54 NO-releasing groups and 54 UDCA units (Dendri-(NO/UDCA)54). For comparison, a lower-generation dendrimer bearing 18 NO-releasing groups and 18 UDCA units (Dendri-(NO/UDCA)18) was also synthesized. The anti-inflammatory activity of these dendrimers was evaluated, showing that the bifunctional dendrimers have an inverse correlation between concentration and anti-inflammatory activity, with an effect dramatically pronounced for Dendri-(NO/UDCA)54 20, which at just 0.25 nM inhibited 76.1% of IL-8 secretion. Data suggest that nanomolar concentrations of these dendrimers aid in releasing NO in a safe and controlled way. This bifunctional dendrimer has great potential as a drug against multifactorial diseases associated with inflammatory processes.

A series of well-defined bifunctional dendrimers bearing one azide and 5,15, and 44 folate termini were synthesizedviathe divergent approach. Poly(N-isopropylacrylamide) homopolymers PNIPAM-7k, PNIPAM-19k, and PNIPAM-64kwere prepared using the reversible addition-fragmentation chain-transfer polymerization(60-67% yield) followed by end functionalization with a cyclooctyne derivative. Agrafting-to approach through strain-promoted azide alkyne cycloaddition between thedendrimers and the PNIPAM afforded a series of dendrimer-b-PNIPAM diblockcopolymers containing folates (G1-11k, G2-30k, and G3-95k). Investigation of the self-assembly process in aqueous media revealed the formation of thermo- and pH-responsivecore-shell spherical micelles within the 70-160 nm size range with low polydispersities.Within the nanoperiodic concept, these dendrimer-b-PNIPAM copolymers behave as S1-type nanoelements that self-assemble into soft:soft spherical nanocompounds with alinear relationship between the molecular weight of the copolymers and thehydrodynamic diameter of the self-assembled nanospheres. The thermo- and pH-responsiveness of the micelles formed by the dendrimer-b-PNIPAM diblock copolymers bearing folates make them promising candidates for targeted drug delivery

Dendronized gold nanoparticles (AuNPs) were synthesized bearing charged peripheral groups. Two novel AB3-type dendrons were synthesized with a thiol group at the focal point followed by their attachment to AuNPs. Dendrons were designed to have nine charged peripheral groups (carboxyl or amine), glycol solubilizing, units and one thiol moiety at the focal point. Both dendrons and all intermediates were synthesized in high yields and characterized by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The amine- and carboxyl-terminated dendrons were used to functionalize gold nanoparticles (AuNPs) previously stabilized with citrate. The nanoparticles’ diameters and their colloidal stability were investigated using dynamic light scattering (DLS). The size and morphology of the dendronized AuNPs were evaluated by scanning electron microscopy (SEM), which revealed individual particles with no aggregation after replacement of citrate by the dendrons, in agreement with the DLS data. The absorption spectroscopy reveals a prominent plasmonic band at 560 nm for all AuNPs. The zeta potential further confirmed the expected charged structures of the dendronized AuNPs. Considering all the physical–chemical properties of the charged dendronized AuNPs developed in this work, these AuNPs might be used as a weapon against multi-drug resistant bacterial infections.

Combination of advantages of ferrocenyl compounds and multifunctional dendrimer scaffold afforded a water-soluble well-defined bifunctional dendrimer with polyamide backbone and thirty two termini: eighteen carboxylic acid groups and eighteen triazolylferrocenyl moieties. The structure of the new dendrimer was thoroughly characterized by nuclear magnetic resonance (NMR) spectroscopy, absorbance spectroscopy in the UV-vis, and MALDI-TOF mass spectrometry. The MALDI-TOF spectrum of the final dendrimer showed the [M](2+) ion peak at 4820.1 m/z unambiguously confirming the successful synthesis of the water-soluble well-defined bifunctional dendrimer. The cytotoxicity of the well-defined bifunctional triazolylferrocenyl dendrimer 4 was evaluated against MCF-7 (breast adenocarcinoma), HeLa (cervical cancer), PC3 (prostate adenocarcinoma), Caco-2 (colorectal cancer), and PNT2 (normal prostate cells) cell lines. The cytotoxicity assays showed that the dendrimer exhibits moderate anticancer activity and targets cancer cells selectively over normal cells.

Carbon nanodots (CNDs) are interesting materials due to their intrinsic fluorescence, electron-transfer properties, and low toxicity. Here, we report a sustainable, cheap, and scalable methodology to obtain CNDs from sugarcane syrup using a domestic microwave oven. The CNDs were characterized by infrared spectroscopy, dynamic light scattering, atomic force microscopy, absorption, and emission spectroscopies. The CNDs have 3 nm in diameter with low polydispersity and are fluorescent. A fluorescent hydrogel–CNDs composite was obtained using gelatin polypeptide as the polymeric matrix. The new hydrogel–CNDs composite was incorporated in the cavities of a double-clad optical fiber using an innovative approach that resulted in a microstructured polymer optical fiber with intrinsic fluorescence. This work shows a promising alternative for the fabrication of fluorescent materials since the CNDs synthesis is sustainable and environmentally friendly. These CNDs might substitute the rare-earth and other heavy metals of high cost and toxicity, which are usually incorporated in double-clad fibers for applications on lasers, amplifiers, and spectroscopy.

The promising field of nanomedicine stimulates a continuous search for multifunctional nanotheranostic systems for imaging and drug delivery. Herein, we demonstrate that application of supramolecular chemistry's concepts in dendritic assemblies can enable the formation of advanced dendrimer-based nanotheranostic devices. A dendrimer bearing 81 triazolylferrocenyl terminal groups adopts a more compact shell-like structure in polar solvents with the ferrocenyl peripheral groups backfolding toward the hydrophobic dendrimer interior, while exposing the more polar triazole moieties as the dendritic shell. Akin to lipids, the compact dendritic structure self-assembles into uniform nanovesicles that in turn self-assemble into larger vesosomes in water. The vesosomes emit green nontraditional intrinsic fluorescence (NTIL), which is an emerging property as there are no classical fluorophores in the dendritic macromolecular structure. This work confirms the hypothesis that the NTIL emission is greatly enhanced by rigidification of the supramolecular assemblies containing heteroatomic subluminophores (HASLs) and by the presence of electron rich functional groups on the periphery of dendrimers. This work is the first one detecting NTIL in ferrocenyl-terminated dendrimers. Moreover, the vesosomes are stable in biological medium, are uptaken by cells, and show cytotoxic activity against cancer cells. Accordingly, the self-organization of these dendrimers into tertiary structures promotes the emergence of new properties enabling the same component, in this case, ferrocenyl group, to function as both antitumoral drug and fluorophore.

Novel folate γ-ferrocene conjugates were synthesized through a regiospecific route, and showed selectivity and enhanced cytotoxicity against Frα-positive malignant cells.

The quest for alternative therapeutic agents with safe and effective profiles is one of the biggest challenges in oncology. Folate-targeted therapy can deliver drugs selectively into malignant cells via the Frα receptor, whereas bioorganometallic chemistry offers potential new drug candidates. Herein, novel folate γ-ferrocene (γ-Fc) conjugates were synthesized through a regiospecific route by reacting amino-terminated glutamate (Glu) γ-Fc residues with pteroyl azide (68–78% yield), and their in vitro anticancer activities were evaluated on human cells. The Fc units were attached to protected Glu residues through different linkers using amide coupling and/or “click” reactions. Cyclic voltammetry and UV-vis measurements showed that the triazole group conjugated to the Fc donates electrons to the ferrous center, which facilitates the oxidation of Fc that is responsible for the antiproliferative activity. These results were confirmed by the higher activity of folate γ-triazoleFc 21, with IC50 values at 25.4 μM (±3.2) on HeLa and 21.7 μM (±0.3) on MCF-7 cells. This compound was up to 4-fold less toxic to healthy PNT2 cells and Frα-negative PC-3 cancer cells. Blocking experiments with an excess of free folic acid inhibited the folate activity suggesting their specific uptake via Frα. Glu residue analogs of folates, but lacking the pteroyl moiety, were much less toxic to cancer cells than folates. Hence, folate γ-Fcs are potential anticancer drug candidates due to their selectivity and enhanced cytotoxicity against Frα-positive malignant cells.

Inflammatory processes are related to a wide variety of diseases with high global impact. Nitric oxide (NO) is an excellent candidate for the treatment of such diseases due to its important anti-inflammatory role in living systems, which is related to its concentration in the cellular medium that in turn depends directly on its release rate from NO releasing compounds. In this work, we synthesized a nitrate-terminated dendrimer and evaluated its anti-inflammatory properties. Remarkably, dendrimer bearing 18 NO-releasing groups was nontoxic, and exhibited anti-inflammatory activity (13.7-27.9% of IL-8 inhibition) throughout the tested concentrations (6.50 X 10(-2) to 4.17 X 10(3) nM of dendrimer; (1.17-7 SO x 10(4) nM of NO-moiety) On the other hand, the NO-releasing monomer was pro-inflammatory at concentrations higher than 62.5 nM. Investigation of the NO-releasing profiles from monomer and dendrimer using real-time NO analyzer NOA confirmed the slow release of NO from the dendrimer. Our results suggest that the NO release from the dendrimer occurs in a controlled fashion, keeping the anti-inflammatory effect of NO even at high concentrations.

Fluorescent carbon nanodots with excitation-dependent emission (blue-green, UV irradiation) were obtained from widely available green sources (orange juice and milk) by microwave-assisted synthesis, a scalable and energetically-efficient approach.

Inflammation is a general pathomechanism associated with numerous diseases of global impact such as many cancers, metabolic disorders, and neurodegenerative and autoimmune diseases. The development of drugs that can treat chronic inflammation, in an effective way and that are well tolerated by the patients, is an active research area that pursues the treatment for hundreds of diseases. Dendrimers recently appeared as a convenient starting point for the design of anti-inflammatory drugs due to its nanosize, well-defined branched structure, multivalency, and versatility. In this work, polyamide dendrimers with 1 ➔ 3 connectivity were synthesized and functionalized with three types of bile acids (BAs): cholic acid (CA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). Functionalization was carried out through strain-promoted alkyne–azide cycloaddition (SPAAC) between an azide dendrimer and cyclooctyne derivatives of bile acids. The cell viability and the anti-inflammatory potential of the bile acid dendrimers were evaluated in vitro and compared with those of the pure BAs. The bile acid dendrimers and pure BAs did not show significant cytotoxicity at the concentrations tested (0.78–5.00 × 10 4 nM) against THP-1 cells. Chenodeoxycholic acid (CDCA) and the corresponding dendrimer dendri-(CDCA) 18 (polyamide dendrimer bearing 18 CDCA moieties) presented the highest anti-inflammatory activity, showing LPS-induced IL-8 release inhibition of 45.3% at 0.78 nM CDCA and 35.5% at 0.43 nM dendri-(CDCA) 18 .

A process for producing fluorescent Carbon Nanodots from sugarcane syrup is reported. The syrup is processed in a domestic microwave oven for 1.5 min, filtered and centrifuged, resulting in an orange stable suspension of nanoparticles capable of emitting visible (green) fluorescence when irradiated by ultraviolet (254 nm). The particles present dimensions ranging from 2 to 6 nm with distribution centered at ~5 nm, and maximum fluorescence intensity at 448 nm (violet) when excited at 360 nm. This work presents a green, fast and low-cost methodology for the obtention of luminescent carbon nanoparticles, with potential applications on optoelectronics, biomedicine, photocatalysis and renewable energy sources areas.

Abstract: Acetalated dextran (Ac-Dex) is a promising pH-sensitive biocompatible and biodegradable polymer for nanomedicine applications. In this work, Ac-Dex nanoparticles were synthesized by two different solvent evaporation methods, the single nanoemulsion and the double nanoemulsion. The Ac-Dex particles were characterized by scanning electron microscopy and the synthesis of highly homogeneous spherical particles was verified. Then, an optical fiber sensor based on quasi-elastic light scattering and comprised of only single-mode optical fibers and standard telecommunication devices showed sensitivity regarding the nanoparticles concentrations and was used for monitoring their degradation over 12 h under pH and temperature conditions of cancerous tissues. The results revealed a well-controlled degradation pattern, corroborating the suitability of the modified polymer to the release of active compounds in a sustainable manner and also demonstrating the applicability of the sensor for the in situ evaluation of the degradation.

Rheology, small-angle X-ray scattering (SAXS), and dynamic light scattering (DLS) analysis, zeta potential measurement, scanning electron microscopy (SEM), and micro-FTIR and absorbance spectroscopy were used to enlighten the controversial literature about LAPONITE® materials. Our data suggest that pristine LAPONITE® in water does not form hydrogels induced by the so-called "house of cards" assembly, but rather forms Wigner glasses governed by repulsive forces. Ionic interactions between anisotropic LAPONITE® nanodiscs, sodium polyacrylate and inorganic salts afforded hydrogels that were transparent, self-standing, moldable, strong, and biocompatible with shear-thinning and self-healing behavior. An extensive study on the role of salts in the gelification process dictates a trend that relates the valence of cations with the viscoelastic properties of the bulk material (G' values follow the trend, monovalent < divalent < trivalent). These hydrogels present G' values up to 5.1 × 104 Pa, which are considered high values for non-covalent hydrogels. Hydrogels crosslinked with sodium phosphate salts are biocompatible, and might be valid candidates for injectable drug delivery systems due to their shear-thinning behavior with rapid self-healing after injection.