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Interactions of oppositely charged macroions in aqueous solution give rise to intriguing aggregation phenomena, resulting in finite-size, long-lived clusters, characterized by a quite narrow size distribution. Particularly, the adsorption of highly charged linear polyelectrolytes on oppositely charged colloidal particles is strongly correlated and some short-range order arises from competing electrostatic interactions between like-charged polymer chains (repulsion) and between polymer chains and particle surface (attraction). In these systems, in an interval of concentrations around the isoelectric point, relatively large clusters of polyelectrolyte-decorated particles form. However, the mechanisms that drive the aggregation and stabilize, at the different polymer/particle ratios, a well-defined size of the aggregates are not completely understood. Nor is clear the role that the correlated polyion adsorption plays in the aggregation, although the importance of “patchy interactions” has been stressed as the possible source of attractive interaction term between colloidal particles. Different models have been proposed to explain the formation of the observed cluster phase. However, a central question still remains unanswered, i.e., whether the clusters are true equilibrium or metastable aggregates. To elucidate this point, in this work, we have investigated the effect of the temperature on the cluster formation. We employed liposomes built up by DOTAP lipids interacting with a simple anionic polyion, polyacrylate sodium salt, over an extended concentration range below and above the isoelectric condition. Our results show that the aggregation process can be described by a thermally activated mechanism. [ABSTRACT FROM AUTHOR]

Polyelectrolyte complexes (PECs), formed via the self-assembly of oppositely charged polysaccharides, are highly valued for their biocompatibility, biodegradability, and hydrophilicity, offering significant potential for biotechnological applications. However, the complex nature and lack of insight at a molecular level into polyelectrolytes conformation and aggregation often hinders the possibility of achieving an optimal control of PEC systems, limiting their practical applications. To address this problem, an in-depth investigation of PECs microscopic structural organization is required. In this work, for the first time, a hybrid approach that combines experimental techniques with atomistic molecular dynamics simulations is used to elucidate, at a molecular level, the mechanisms underlying the aggregation and structural organization of complexes formed by gellan and chitosan, i.e. PECs commonly used in food technology. This combined analysis reveals a two-step complexation process: gellan initially self-assembles into a double-helix structure, subsequently surrounded and stabilized by chitosan via electrostatic interactions. Furthermore, these results show that complexation preserves the individual conformation and intrinsic functionality of both polyelectrolytes, thereby ensuring the efficacy of the PECs in biotechnological applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Satureja montana essential oil is a natural substance able to inhibit the growth of several pathogens. This antimicrobial effect is often attributed to its ability to penetrate cellular structures and disrupt them. Although these properties are recognized as playing a key role in the mechanism of action of this substance, many unresolved issues still exist, and fundamental studies focused on such aspects are scarce. In this framework, we investigated the interaction of SEO with lipid monolayers, which represent simplified models of cell membranes, using the Langmuir monolayer technique, complemented by fluorescence anisotropy and differential scanning calorimetry on lipid bilayers. By focusing on packing conditions that approximate those of biological membranes and using lipids with different polar heads and structures, such as the ones occurring in bacterial membranes, we aim to clarify the effect of this essential oil on the lipid membrane. Our results show that Satureja montana essential oil consistently manages to insert into the membrane and interfere with the lipid-lipid interactions, thereby altering the lipid packing and significantly increasing the membrane fluidity, depending on the oil concentration and the nature of the lipid.

It has been shown recently, without an explanation of the possible molecular mechanisms involved, that 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic (EPPS) acid effectively protects from the neurotoxicity induced by oligomers and plaques formed by the protein amyloid-β protein. Here we report the same protective effect, obtained in vitro (HT22-diff cell line) and ex vivo (hippocampal slices) models, against amyloid neurotoxicity induced by oligomers of salmon Calcitonin (sCT), which has been shown to be a good model for the study of neurodegenerative diseases. Based on biophysical studies focusing on the protein aggregation kinetic and the interaction of the aggregates with model membranes, we propose a possible molecular mechanism underlying the protective effects. Taken together, our results indicate that EPPS is able to counteract the direct association (primary aggregation) of harmless low-molecular weight aggregates (dimers and trimers) or their aggregation catalysed by surfaces present in the solution (secondary aggregation). Thus, EPPS stabilizes harmless aggregates and hinders the formation of toxic and metastable prefibrillar oligomers. Overall, our data demonstrate that EPPS is an excellent drug candidate for the treatment of neurodegeneration due to misfolded proteins, such as Alzheimer's or Parkinson's disease., (© 2024. The Author(s).)

Carbon dots (CDs) are an emerging class of carbon nanoparticles, which for their characteristics have found applications in many fields such as catalysis, materials and biomedicine. Within this context, the application of CDs as antibacterial agents has received much attention in very recent years, while their use as antifungal nanoparticles has been scarcely investigated. Here we report a systematic investigation of the surface functional groups of CDs to study their influence on these nanoparticles' against Candida albicans. Three classes of CDs have been synthesised and fully characterized. A thorough in vitro and in vivo biological screening against C. albicans was performed to test their antifungal, antiadhesion and antibiofilm formation activities. Moreover, the interaction with C. albicans cells was investigated by microscopic analysis. Our results evidence how the presence of a positively polarised surface results crucial for the internalization into COS-7 cells. Positively charged nanoparticles were also able to inhibit adhesion and biofilm formation, to interact with the cellular membrane of C. albicans, and to increase the survival of G. mellonella infected larvae after the injection with positive nanoparticles. The antifungal activity of CDs and their extremely low toxicity may represent a new strategy to combat infections sustained by C.albicans., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The interplay of soft responsive particles, such as microgels, with nanoparticles (NPs) yields highly versatile complexes that show great potential for applications, ranging from plasmonic sensing to catalysis and drug delivery. However, the microgel-NP assembly process has not been investigated so far at the microscopic level, thus hindering the possibility of designing such hybrid systems a priori. In this work, we combine state-of-the-art numerical simulations with experiments to elucidate the fundamental mechanisms taking place when microgel-NP assembly is controlled by electrostatic interactions and the associated effects on the structure of the resulting complexes. We find a general behavior where, by increasing the number of interacting NPs, the microgel deswells up to a minimum size after which a plateau behavior occurs. This occurs either when NPs are mainly adsorbed to the microgel corona via the folding of the more external chains or when NPs penetrate inside the microgel, thereby inducing a collective reorganization of the polymer network. By varying microgel properties, such as fraction of cross-linkers or charge, as well as NP size and charge, we further show that the microgel deswelling curves can be rescaled onto a single master curve, for both experiments and simulations, demonstrating that the process is entirely controlled by the charge of the whole microgel-NP complex. Our results thus have a direct relevance in fundamental materials science and offer novel tools to tailor the nanofabrication of hybrid devices of technological interest.

Antibiotic resistance due to bacterial biofilm formation is a major global health concern that makes the search for new therapeutic approaches an urgent need. In this context,, trans -resveratrol (RSV), a polyphenolic natural substance, seems to be a good candidate for preventing and eradicating biofilm-associated infections but its mechanism of action is poorly understood. In addition, RSV suffers from low bioavailability and chemical instability in the biological media that make its encapsulation in delivery systems necessary. In this work, the anti-biofilm activity of free RSV was investigated on Staphylococcus aureus and, to highlight the possible mechanism of action, we studied the anti-adherence activity and also the cell wall damage on a MRSA strain. Free RSV activity was compared to that of RSV loaded in liposomes, specifically neutral liposomes (L = DOPC/Cholesterol) and cationic liposomes (LG = DOPC/Chol/GLT1) characterized by a galactosylated amphiphile (GLT1) that promotes the interaction with bacteria. The results indicate that RSV loaded in LG has anti-adherence and anti-biofilm activity higher than free RSV. On the other side, free RSV has a higher bacterial-growth-inhibiting effect than encapsulated RSV and it can damage cell walls by creating pores; however, this effect can not prevent bacteria from growing again. This RSV ability may underlie its bacteriostatic activity.

Despite the significant contribution of titanium and its alloys for hard tissue regenerative medicine, some major issues remain to be solved. Implants' long-term stability is threatened by poor osseointegration. Moreover, bacterial adhesion and excessive inflammatory response are also to be considered in the design of a device intended to be integrated into the human body. Here, a cerium mixed oxide (CeO x ) coating was realized on pristine and nanotubular-structured Ti and Ti6Al4V surfaces using a simple layer-by-layer drop-casting technique. Bioactivity, resistance in simulated inflammatory conditions, and bactericidal capacity were evaluated as a function of morphological surface characteristics combined with the cerium quantity deposited. The results obtained suggest that the presence of CeO x on the surfaces with nanotubes enhanced osseointegration, while on the non-nanostructured surfaces, this coating improved resistance under oxidative stress and provided excellent antibacterial properties.

Mycobacterium abscessus (Mabs) is a dangerous non-tubercular mycobacterium responsible for severe pulmonary infections in immunologically vulnerable patients, due to its wide resistance to many different antibiotics which make its therapeutic management extremely difficult. Drug nanocarriers as liposomes may represent a promising delivery strategy against pulmonary Mabs infection, due to the possibility to be aerosolically administrated and to tune their properties in order to increase nebulization resistance and retainment of encapsulated drug. In fact, liposome surface can be modified by decoration with mucoadhesive polymers to enhance its stability, mucus penetration and prolong its residence time in the lung. The aim of this work is to employ Chitosan or ε-poly-L-lysine decoration for improving the properties of a novel liposomes composed by hydrogenated phosphatidyl-choline from soybean (HSPC) and anionic 1,2-Dipalmitoyl-sn-glycero-3-phosphorylglycerol sodium salt (DPPG) able to entrap Rifampicin. A deep physicochemical characterization of polymer-decorated liposomes shows that both polymers improve mucoadhesion without affecting liposome features and Rifampicin entrapment efficiency. Therapeutic activity on Mabs-infected macrophages demonstrates an effective antibacterial effect of ε-poly-L-lysine liposomes with respect to chitosan-decorated ones. Altogether, these results suggest a possible use of ε-PLL liposomes to improve antibiotic delivery in the lung.

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration.

Laser Transmission Spectroscopy (LTS) is an experimental technique able to determine the particle number concentration and the size of colloidal suspensions by a single measurement of the transmittance of a laser beam through the suspension of particles as a function of the wavelength. In this protocol, we show that LTS represents a unique and powerful tool to investigate suspensions of liposomes, where the precise quantification of the number concentration is particularly relevant for the complete definition of the colloidal properties of the suspension. We study a model formulation of Soy-PC:Chol liposomes and we validate LTS results by comparison with High-Performance Liquid Chromatography determination of lipid mass. Then LTS protocols is applied to state-of-art liposomal nanocarrier suspensions. We explain details of data analysis to obtain the particle number concentration by using the Lambert-Beer law and by calculating the extinction cross section, within the framework of Mie theory for spherical vesicles. We also determine the liposome radius and compare it with the hydrodynamic radius measured by Dynamic Light Scattering. As future perspective, we aim to extend LTS analysis to other nanostructures with different geometries and to contribute to the development of new quantitative strategies for the accurate characterization of nanocarriers and other nanoparticles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Extrinsic chemiluminescence can be an efficient tool for determining pesticides and fungicides, which do not possess any intrinsic fluorescent signal. On this basis, (3-aminopropyl) trimethoxysilane (APTMS)-coated ZnO (APTMS@ZnO) was synthesized and tested as an extrinsic probe for the fungicide penconazole. Several synthetic routes were probed using either a one-pot or two-steps method, in order to ensure both a green synthetic pathway and a good signal variation for the penconazole concentration. The synthesized samples were characterized using X-ray diffraction (XRD), infrared (IR), Raman and ultraviolet-visible (UV-Vis) spectroscopy, scanning electron microscopy (SEM) imaging and associated energy-dispersive X-ray (EDX) analysis. The average size of the synthesized ZnO nanoparticles (NPs) is 54 ± 10 nm, in line with previous preparations. Of all the samples, those synthesized in two steps, at temperatures ranging from room temperature (RT) to a maximum of 40 °C, using water solvent (G-APTMG@ZnO), appeared to be composed of nanoparticles, homogeneously coated with APTMS. Chemiluminescence tests of G-APTMG@ZnO, in the penconazole concentration range 0.7-1.7 ppm resulted in a quenching of the native signal between 6% and 19% with a good linear response, thus indicating a green pathway for detecting the contaminant. The estimated detection limit (LOD) is 0.1 ± 0.01 ppm.

Hypothesis: Self-assembling molecular structures responding to light stimulus are appealing for applications as sensing and drug delivery. Supramolecular nanotubes have a relevant potential in nanotechnology as they can be used to encapsulate different loads like drugs, biological macromolecules, and nanomaterials. In addition, they are suitable elements for novel supracolloidal materials. Structural responses of supramolecular nanotubes to non-invasive stimuli are very much desired to enable controlled release of the encapsulated guests and to provide these recently developed new materials with an external trigger. Here, we describe the formation of well-defined, single wall tubules that interconvert into twisted ribbons upon UV-light exposure in aqueous environment. The structures are provided by self-assembly of an azobenzene substituted cholic acid, a biological surfactant belonging to the family of bile acids. The azobenzene group allows for the light responsiveness of the molecular packing. Concurrently the steroidal moieties assure both chiral features and extensive hydrophobic interactions for time and temperature resistant aggregates., Experiments: The molecular packing interconversion was followed by circular dichroism. Microscopy, small angle X-ray scattering and light scattering measurements demonstrated the drastic morphological variation upon irradiation. A model of the molecular arrangement within the tubular walls was suggested based on the circular dichroism spectra simulation., Findings: Innovatively, the molecular design reported in our work allows for encoding in the same light responsive system multiple desirable features (e.g. bio-origin, temperature resistance and chirality of the aggregates). Such combination of properties, never reported before for a single molecule, might be relevant for the realization of robust, stimuli-responsive bio-vectors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Amyloid-β peptide (Aβ) aggregates are known to be correlated with pathological neurodegenerative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro Aβ42 fibril formation in the presence of cortisol at different relative concentrations. The thioflavin T fluorescence assay allowed us to monitor the fibril formation kinetics, while a morphological characterization of the aggregates was obtained by atomic force microscopy. Moreover, infrared absorption spectroscopy was exploited to investigate the secondary structure changes along the fibril formation path. Molecular dynamics calculations allowed us to understand the intermolecular interactions with cortisol. The combined results demonstrated the influence of cortisol on the fibril formation process: indeed, at cortisol-Aβ42 concentration ratio (ρ) close to 0.1 a faster organization of Aβ42 fragments into fibrils is promoted, while for ρ = 1 the formation of fibrils is completely inhibited.

Preparation and characterization of a block-like l,d-octapeptide-dextran conjugate DEX 29 -(l-Val-d-Val) 4 self-assembling into nanowire structures is reported. The conjugate was prepared by solid phase click-chemistry on an alkyne group N-terminus functionalized peptide with a regularly alternating enantiomeric sequence. Low molecular weight dextran (X n  = 29) with moderately low dispersity (1.30) was prepared by controlled acid hydrolysis and dialysis with selected cut-off and functionalized with an azido group on the reducing end by reductive amination. The strong hydrogen bonds and hydrophobic interactions of the (l-Val-d-Val) 4 linear peptide drive the conjugate to self-assemble into long (0.1-1 μm) nanowires. To our knowledge, this is the first example of a peptide-polysaccharide conjugate that can self-assemble into a nanowire architecture., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Multi-responsive nanomaterials based on the self-limited assembly of plasmonic nanoparticles are of great interest due to their widespread employment in sensing applications. We present a thorough investigation of a hybrid nanomaterial based on the protein-mediated aggregation of gold nanoparticles at varying protein concentration, pH and temperature. By combining Small Angle X-ray Scattering with extinction spectroscopy, we are able to frame the morphological features of the formed fractal aggregates in a theoretical model based on patchy interactions. Based on this, we established the main factors that determine the assembly process and their strong correlation with the optical properties of the assemblies. Moreover, the calibration curves that we obtained for each parameter investigated based on the extinction spectra point out to the notable flexibility of this nanomaterial, enabling the selection of different working ranges with high sensitivity. Our study opens for the rational tuning of the morphology and the optical properties of plasmonic assemblies to design colorimetric sensors with improved performances.

The C1858T variant of the protein tyrosine phosphatase N22 ( PTPN22 ) gene is associated with pathophysiological phenotypes in several autoimmune conditions, namely, Type 1 diabetes and autoimmune thyroiditis. The R620W variant protein, encoded by C1858T, leads to a gain of function mutation with paradoxical reduced T cell activation. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes, LiposiRNA) that selectively inhibit variant allele expression. In this manuscript, we functionalize lipoplexes carrying siRNA for variant C1858T with a high affinity ligand of Siglec-10 (Sig10L) coupled to lipids resulting in lipoplexes (LiposiRNA-Sig10L) that enhance delivery to Siglec-10 expressing immunocytes. LiposiRNA-Sig10L lipoplexes more efficiently downregulated variant C1858T PTPN22 mRNA in PBMC of heterozygous patients than LiposiRNA without Sig10L. Following TCR engagement, LiposiRNA-Sig10L more significantly restored IL-2 secretion, known to be paradoxically reduced than in wild type patients, than unfunctionalized LiposiRNA in PBMC of heterozygous T1D patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arena, Belcastro, Ceccacci, Petrini, Conti, Pagliarosi, Giorda, Sennato, Schiaffini, Wang, Paulson, Mancini and Fierabracci.)

The tattoos removal has become an issue upon spread of the tattooing practice worldwide and hindsight regrets. Lasers are typically used for the purpose, though some colours such as green are considered "recalcitrant" to the treatment. In the current investigation, we aim at determining the efficacy of removal of a green ink water dispersion, using 5 laser treatments: Nd:YAG nano- and picosecond lasers in normal and array mode and Ruby nanosecond laser, keeping the total irradiated energy constant. The UV-Vis spectroscopy of the treated samples indicate that Nd:YAG picosecond laser is most effective, and the Ruby nanosecond laser is the least efficient. Fragment compounds generated from the pigment and siloxanes are common to all treatments, whereas hydrocarbon emerge by a larger amount upon Nd:YAG nanosecond treatment. Fibres are formed upon picosecond treatments and when operating in array mode, and lamellae are achieved by Ruby nanosecond laser treatment. Residual particles suspensions are very heterogeneous upon nanosecond treatments., (© 2022. The Author(s).)

Glucosylated liposomes composed of the natural saturated phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and a cationic amphiphile featuring a glucosyl moiety (GL4), have been developed for delivering the antimicrobial trans-Resveratrol (RSV) to S. epidermidis, characterized by carbohydrate-specific adhesins able to recognize glucose. The cationic derivative of cholesterol, DC-Chol, was also included in liposome formulations, alone or in combination with GL4, in order to explore the role of both cationic charge and sugar moiety in the interaction of liposomes with bacterial cells. RSV was included inside glucosylated cationic liposomes by the thin film method, coupled with either extrusion or sonication; liposome mean diameter, polydispersity index, surface charge, RSV entrapment efficiency and concentration have been measured by DLS, electrophoretic mobility, and HPLC. The antimicrobial activity of RSV-loaded liposomes was evaluated by monitoring the bacterial growth curves of two cell lines of Staphylococcus epidermidis, a slime positive strain (i.e. a strain able to form a biofilm) and a slime negative one. Results point out that, when the glucosylamphiphile GL4 is included in the formulation, only the extrusion protocol allows obtaining monodisperse liposomes with high RSV entrapment efficiency. The mean diameters of empty and resveratrol-loaded liposomes are all around 120-140 nm and size distribution are narrow, except for samples including GL4 at 5 molar percentage. Here the higher polydispersity index may be the indication of the occurrence of a restructuring phenomenon. The microbiological tests put in evidence a different response of the two bacterial cell lines to liposome treatments, in fact, the slime negative bacterial cells, that are not able to produce the extracellular polymeric substances, are more susceptible to the cationic charge of the liposomes and to the detergent effect of GL4. The most interesting results concern DPPC/Chol/GL4 liposomes on the slime positive strain: this formulation, non-toxic in itself, displays an enhanced antibacterial efficacy with respect to free RSV, killing bacteria even at concentration tenfold under the MIC., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Surface free energy (SFE) of titanium surfaces plays a significant role in tissue engineering, as it affects the effectiveness and long-term stability of both active coatings and functionalization and the establishment of strong bonds to the newly growing bone. A new contact-mechanics methodology based on high-resolution non-destructive elastic contacting nanoindentation is applied here to study SFE of micro- and nano-structured titanium surfaces, right after their preparation and as a function of exposure to air. The effectiveness of different surface treatments in enhancing SFE is assessed. A time-dependent decay of SFE within a few hours is observed, with kinetics related to the sample preparation. The fast, non-destructive method adopted allowed for SFE measurements in very hydrophilic conditions, establishing a reliable comparison between surfaces with different properties.

Isoniazid (INH) is one of the primary drugs used in tuberculosis treatment and its encapsulation in liposomal vesicles can both improve its therapeutic index and minimize toxicity. Here we consider mixtures of hydrogenated soy phosphatidylcholine-phosphatidylglycerol (HSPC-DPPG) to get novel biocompatible liposomes for INH delivery. We determined INH encapsulation efficiency by coupling for the first time UV and Laser Transmission Spectroscopy and we showed that HSPC-DPPG liposomes can load more INH than expected from simple geometrical arguments, thus suggesting the presence of drug-lipid association. To focus on this aspect, which has never been explored in liposomal formulations, we employed several complementary techniques, such as dynamic and static light scattering, calorimetry and surface pressure measurements on lipid monolayers. We find that INH-lipid interaction increases the entrapment capability of liposomes due to INH adsorption. Moreover, the preferential INH-HSPC dipole-dipole interaction promotes the modification of lipid ordering, favoring the formation of HSPC-richer domains in excess of DPPG. Our findings highlight how investigating the fundamental aspects of drug-lipid interactions is of paramount importance for the optimal design of liposomal nanocarriers., (Copyright © 2021 Elsevier B.V. All rights reserved.)

It is widely acknowledged that mammalian exosomes (or extracellular vesicles), have a key role in intercellular communication, owing to the presence of various bioactive molecules such as lipids, proteins, and microRNAs within their inner compartment. Most recently, the discovery of extracellular vesicles isolated from edible plants (such as vegetables and fruits) and their similarity in terms of size and content with exosomes has opened new perspectives on possible intercellular communication and regulation of important biological processes in which these vesicles are involved. It is also well-known that a balanced diet rich of fruits and vegetables (i.e., the Mediterranean diet) can contribute to maintain a "healthy gut" by preserving the intestinal epithelial barrier integrity and avoid that inflammatory stimuli that can alter homeostasis. In our study, we optimized a method to isolate extracellular vesicles from the orange juice (Citrus sinensis) (CS-EVs), and we characterized their morphology and behavior when in contact with the intestinal epithelium. We showed that CS-EVs are stable in a simulated gastrointestinal environment and are absorbed by intestinal cells without toxic effects, as expected. Furthermore, we demonstrated that CS-EVs can alter the gene expression of several genes involved in inflammation (i.e., ICAM1 and HMOX-1 ) and tight junctions (i.e., OCLN, CLDN1 , and MLCK ), contributing to limit inflammatory stimuli and restore a functional barrier by increasing the tight junction OCLN protein. Therefore, our study emphasizes the relevant role of fruit-derived extracellular vesicles in modulating important biological processes and maintaining a healthy intestinal epithelium, ultimately promoting human health and well-being., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bruno, Paolini, D'Oria, Sarra, Sennato, Bordi and Masotti.)

Background: There is a huge body of literature data on ZnOnanoparticles (ZnO NPs) toxicity. However, the reported results are seen to be increasingly discrepant, and deep comprehension of the ZnO NPs behaviour in relation to the different experimental conditions is still lacking. A recent literature overview emphasizes the screening of the ZnO NPs toxicity with more than one assay, checking the experimental reproducibility also versus time, which is a key factor for the robustness of the results. In this paper we compared high-throughput real-time measurements through Electric Cell-substrate Impedance-Sensing (ECIS®) with endpoint measurements of multiple independent assays., Results: ECIS-measurements were compared with traditional cytotoxicity tests such as MTT, Neutral red, Trypan blue, and cloning efficiency assays. ECIS could follow the cell behavior continuously and noninvasively for days, so that certain long-term characteristics of cell proliferation under treatment with ZnO NPs were accessible. This was particularly important in the case of pro-mitogenic activity exerted by low-dose ZnO NPs, an effect not revealed by endpoint independent assays. This result opens new worrisome questions about the potential mitogenic activity exerted by ZnO NPs, or more generally by NPs, on transformed cells. Of importance, impedance curve trends (morphology) allowed to discriminate between different cell death mechanisms (apoptosis vs autophagy) in the absence of specific reagents, as confirmed by cell structural and functional studies by high-resolution microscopy. This could be advantageous in terms of costs and time spent. ZnO NPs-exposed A549 cells showed an unusual pattern of actin and tubulin distribution which might trigger mitotic aberrations leading to genomic instability., Conclusions: ZnO NPs toxicity can be determined not only by the intrinsic NPs characteristics, but also by the external conditions like the experimental setting, and this could account for discrepant data from different assays. ECIS has the potential to recapitulate the needs required in the evaluation of nanomaterials by contributing to the reliability of cytotoxicity tests. Moreover, it can overcome some false results and discrepancies in the results obtained by endpoint measurements. Finally, we strongly recommend the comparison of cytotoxicity tests (ECIS, MTT, Trypan Blue, Cloning efficiency) with the ultrastructural cell pathology studies., (© 2021. The Author(s).)

Water pollution caused by hexavalent chromium (Cr(VI)) ions represents a serious hazard for human health due to the high systemic toxicity and carcinogenic nature of this metal species. The optical sensing of Cr(VI) through specifically engineered nanomaterials has recently emerged as a versatile strategy for the application to easy-to-use and cheap monitoring devices. In this study, a one-pot oxidative method was developed for the cage opening of C 60 fullerene and the synthesis of stable suspensions of N-doped carbon dots in water-THF solutions (N-CDs-W-THF). The N-CDs-W-THF selectively showed variations of optical absorbance in the presence of Cr(VI) ions in water through the arising of a distinct absorption band peaking at 550 nm, i.e., in the transparency region of pristine material. Absorbance increased linearly, with the ion concentration in the range 1-100 µM, thus enabling visual and ratiometric determination with a limit of detection (LOD) of 300 nM. Selectivity and possible interference effects were tested over the 11 other most common heavy metal ions. The sensing process occurred without the need for any other reactant or treatment at neutral pH and within 1 min after the addition of chromium ions, both in deionized and in real water samples.

Thermoresponsive microgels are one of the most investigated types of soft colloids, thanks to their ability to undergo a Volume Phase Transition (VPT) close to ambient temperature. However, this fundamental phenomenon still lacks a detailed microscopic understanding, particularly regarding the presence and the role of charges in the deswelling process. This is particularly important for the widely used poly( N -isopropylacrylamide)-based microgels, where the constituent monomers are neutral but charged groups arise due to the initiator molecules used in the synthesis. Here, we address this point combining experiments with state-of-the-art simulations to show that the microgel collapse does not happen in a homogeneous fashion, but through a two-step mechanism, entirely attributable to electrostatic effects. The signature of this phenomenon is the emergence of a minimum in the ratio between gyration and hydrodynamic radii at the VPT. Thanks to simulations of microgels with different cross-linker concentrations, charge contents, and charge distributions, we provide evidence that peripheral charges arising from the synthesis are responsible for this behavior and we further build a universal master curve able to predict the two-step deswelling. Our results have direct relevance on fundamental soft condensed matter science and on applications where microgels are involved, ranging from materials to biomedical technologies., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell-cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell-cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1α and IL1β potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche.

Treatment of pulmonary infections caused by Mycobacterium abscessus are extremely difficult to treat, as this species is naturally resistant to many common antibiotics. Liposomes are vesicular nanocarriers suitable for hydrophilic and lipophilic drug loading, able to deliver drugs to the target site, and successfully used in different pharmaceutical applications. Moreover, liposomes are biocompatible, biodegradable and nontoxic vesicles and nebulized liposomes are efficient in targeting antibacterial agents to macrophages. The present aim was to formulate rifampicin-loaded liposomes (RIF-Lipo) for lung delivery, in order to increase the local concentration of the antibiotic. Unilamellar liposomal vesicles composed of anionic DPPG mixed with HSPC for rifampicin delivery were designed, prepared, and characterized. Samples were prepared by using the thin-film hydration method. RIF-Lipo and unloaded liposomes were characterized in terms of size, ζ-potential, bilayer features, stability and in different biological media. Rifampicin's entrapment efficiency and release were also evaluated. Finally, biological activity of RIF-loaded liposomes in Mycobacterium abscessus-infected macrophages was investigated. The results show that RIF-lipo induce a significantly better reduction of intracellular Mycobacterium abscessus viability than the treatment with free drug. Liposome formulation of rifampicin may represent a valuable strategy to enhance the biological activity of the drug against intracellular mycobacteria.

Comparative laser and thermal treatments were carried out on PG36, a green phthalocyanine-based pigment, permitted in European countries where legislation on tattoo composition was issued. Prior to the treatments, PG36 was characterized by SEM imaging, EDX, IR and UV-Vis spectroscopies, revealing an excess of Si and C and O as compared to the pure halogenated Cu-phthalocyanine. Laser treatments were carried out with a Nd:YAG device applied to H 2 O and propan-2-ol dispersions. Pyrolysis and calcinations were carried out in air or under N 2 flow. The outcome of the different procedures was analyzed by UV-Vis spectroscopy, GC-mass spectrometry, X-ray diffraction of the solid residues, SEM microscopy and dynamic light scattering. The comparative analysis indicated the production of different fragment compounds depending on the treatment, (pyrolysis or laser), and, to some extent, to the solvent of the dispersion, with pyrolysis generating a larger number of hazardous compounds. Hydrocarbons and cyclic siloxanes present as additives in PG36 were stable or degraded depending on the treatment. The morphology of the products is also treatment-dependent with nanoparticles < 20 nm and fibers being produced upon laser treatments only. Based on the experimental findings, the equivalence of laser and thermal treatments is evaluated.

The growing demand for innovative means in biomedical, therapeutic and diagnostic sciences has led to the development of nanomedicine. In this context, naturally occurring tubular nanostructures composed of rolled sheets of alumino-silicates, known as halloysite nanotubes, have found wide application. Halloysite nanotubes indeed have surface properties that favor the selective loading of biomolecules. Here, we present the first, to our knowledge, structural study of DNA-decorated halloysite nanotubes, carried out with nanometric spatially-resolved infrared spectroscopy. Single nanotube absorption measurements indicate a partial covering of halloysite by DNA molecules, which show significant structural modifications taking place upon loading. The present study highlights the constraints for the use of nanostructured clays as DNA carriers and demonstrates the power of super-resolved infrared spectroscopy as an effective and versatile tool for the evaluation of immobilization processes in the context of drug delivery and gene transfer.

PNIPAm microgels synthesized via free radical polymerization (FRP) are often considered as neutral colloids in aqueous media, although it is well known, since the pioneering works of Pelton and coworkers, that the vanishing electrophoretic mobility characterizing swollen microgels largely increases above the lower critical solution temperature (LCST) of PNIPAm, at which microgels partially collapse. The presence of an electric charge has been attributed to the ionic initiators that are employed when FRP is performed in water and that stay anchored to microgel particles. Combining dynamic light scattering (DLS), electrophoresis, transmission electron microscopy (TEM) and atomic force microscopy (AFM) experiments, we show that collapsed ionic PNIPAm microgels undergo large mobility reversal and reentrant condensation when they are co-suspended with oppositely charged polyelectrolytes (PE) or nanoparticles (NP), while their stability remains unaffected by PE or NP addition at lower temperatures, where microgels are swollen and their charge density is low. Our results highlight a somehow double-faced electrostatic behavior of PNIPAm microgels due to their tunable charge density: they behave as quasi-neutral colloids at temperature below LCST, while they strongly interact with oppositely charged species when they are in their collapsed state. The very similar phenomenology encountered when microgels are surrounded by polylysine chains and silica nanoparticles points to the general character of this twofold behavior of PNIPAm-based colloids in water.

In this chapter we describe: (1) the procedure for the synthesis of four single chain bolaamphiphiles, displaying chains of 12, 16, 20 and 30 methylene units and triphenylphosphonium moieties as headgroups (TPP1-TPP4); (2) the methods used to characterize TPP1-TPP4 spontaneous aggregation in aqueous solution. We illustrate the determination of Krafft point and cac by conductivity measurements and the procedures used to investigate dimensions, morphology, and stability by dynamic and dielectrophoretic laser light scattering, dialysis, transmission electron microscopy, and Raman spectroscopy measurements.

Since tattoos became overwhelmingly fashionable worldwide, the demand for removal has proportionally increased, Nd:YAG Q-switch laser being the most commonly used tool for the purpose. In this framework we investigated the composition and products of laser treatment of green tattoo ink, the Green Concentrate from Eternal. The ink characterization has been carried out by IR, UV-Vis, EDX spectroscopies, and SEM imaging. It revealed the presence of the pigment PG7, rather than PG36 as reported on the bottle label, along with non-fully halogenated analogues. The morphology is an extended sheath with embedded grains. Subsequent laser treatments were performed on both dried and extracted inks, dispersed either in water or in propan-2-ol, chosen for their different polarities, as it is the case in the skin layers. The products were analyzed by gas chromatography-mass spectrometry, UV-Vis spectroscopy, SEM imaging, and dynamic light scattering. The outcome is a complex fragmentation pattern that depends both on the solvent and on the initial aggregation state. The fragment compounds are toxic at various degrees according to the Classification Labelling and Packaging regulations. Several shapes of aggregates are produced as an effect of both downsizing and re-aggregation, with potentially harmful aspect ratios.

Noncovalent DNA functionalization is one of the most used routes for the easy dispersion of carbon nanotubes (CNTs) yielding DNA-CNTs complexes with promising applications. Definition of the structure of adsorbed DNA is crucial, but the organization of polymer at the carbon interface is far from being understood. In comparison to single-walled nanotubes, not much effort has been devoted to assessing the structure of the adsorbed DNA on multiwalled carbon nanotubes (MWCNTs), where their metallic nature, large size, and polydispersity represent serious obstacles for both experimental and theoretical studies. As a contribution to fill this lack in these aspects, we investigated DNA-MWCNT complexes by dielectric spectroscopy (DS) which is sensitive to even small changes in the charge distribution at charged interfaces and was largely employed in studying the electric and conformational properties of polyelectrolytes, such as DNA, in aqueous solutions and at interfaces. The dielectric relaxation in the MHz range is the signature of DNA adsorption on CNTs and sheds light on its conformational properties. A detailed analysis of the conductivity of the DNA-MWCNT suspensions unequivocally proves that DNA is adsorbed in a single-stranded conformation while excess DNA reassociates without interfering with the stability of the complexes.

Dynamic Light Scattering (DLS), Small Angle X-ray Scattering (SAXS) and Transmission Electron Microscopy (TEM) are physical techniques widely employed to characterize the morphology and the structure of vesicles such as liposomes or human extracellular vesicles (exosomes). Bacterial extracellular vesicles are similar in size to human exosomes, although their function and membrane properties have not been elucidated in such detail as in the case of exosomes. Here, we applied the above cited techniques, in synergy with the thermotropic characterization of the vesicles lipid membrane using a turbidimetric technique to the study of vesicles produced by Gram-negative bacteria (Outer Membrane Vesicles, OMVs) grown at different temperatures. This study demonstrated that our combined approach is useful to discriminate vesicles of different origin or coming from bacteria cultured under different experimental conditions. We envisage that in a near future the techniques employed in our work will be further implemented to discriminate complex mixtures of bacterial vesicles, thus showing great promises for biomedical or diagnostic applications., (Copyright © 2020 Sarra, Celluzzi, Bruno, Ricci, Sennato, Ortore, Casciardi, Del Chierico, Postorino, Bordi and Masotti.)

Biomolecule derivatives are transversally used in nanotechnology. Deciphering their aggregation behavior is a crucial issue for the rational design of functional materials. To this end, it is necessary to build libraries of selectively functionalized analogues and infer general rules. In this work we enrich the highly applicative oriented collection of steroid derivatives, by reporting a rare example of C-12 selectively modified bile salt. While nature often exploits such position to encode functions, it is unusual and not trivial to prepare similar analogues in the laboratory. The introduction of a tert-butyl phenyl residue at C-12 provided a molecule with a self-assembly that remarkably switched from rigid pole-like structures to twisted ribbons at a biologically relevant critical temperature (∼25 °C). The system was characterized by microscopy and spectroscopy techniques and compared with the C-3 functionalized analogue. The twisted ribbons generate samples with a gel texture and a viscoelastic response. The parallel analysis of the two systems suggested that the observed thermoresponsive self-assemblies occur at similar critical temperatures and are probably dictated by the nature of the substituent, but involve aggregates with different structures depending on position and orientation of the substituent. This study highlights the self-assembly properties of two appealing thermoresponsive systems. Moreover, it adds fundamental insights hereto missing in the investigations of the relation between self-assembly and structure of synthetic steroids, which are valuable for the rational design of steroidal amphiphiles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lignin isolated from beech sawdust was used for the preparation of lignin nanoparticles (LNPs) with entrapped essential oil (EO) from cinnamon bark ( Cinnamomum zeylanicum Blume), common thyme ( Thymus vulgaris L.), and wild thyme ( Thymus serpyllum L.) using a fast antisolvent method. Analysis of EO-loaded LNPs by pyrolysis-gas chromatography-mass spectrometry and Fourier transform infrared spectroscopy confirmed molecular interaction between EOs and LNPs. Quantification of EO incorporation into the LNPs and their in vitro release profiles were assessed by reversed phase high-performance liquid chromatography. Utilized EOs were, to different extents, successfully entrapped inside LNPs, which were attributed to extensive π-stacking between aromatic compounds in EOs like cinnamaldehyde, thymol, and carvacrol on one side and aromatic lignin units on the other side. In vitro release of common thyme and wild thyme EOs from EO-loaded LNPs was strongly delayed compared to the use of pure oil, giving a promising outlook for the development of new bio-based biocide delivery systems for wood preservation., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Background: The advent of 3D printing technology allowed the realization of custom devices that can be used not only in the everyday life but also in the nanotechnology and biomedical fields. In nanotechnology, the use of bi-dimensional nanostructures based on carbon nanotubes, generally referred as buckypapers, have received considerable attention for their versatility and potential application in many biomedical fields. Unfortunately, buckypapers are extremely hydrophobic and cannot be used in aqueous media to culture cells., Methods: A polymeric device able to accommodate buckypapers and facilitate cell growth was fabricated by using 3D printing technology. We imparted hydrophilicity to buckypapers by coating them with polyamidoamine (PAMAM) dendrimers., Results: We found that by using novel techniques such as polymer coating the buckypaper hydrophilicity increased, whereas the use of 3D printing technology allowed us to obtain custom devices that have been used to culture cells on buckypapers for many days. We characterized in details the morphology of these structures and studied for the first time the kinetic of cell proliferation. We found that these scaffolds, if properly functionalized, are suitable materials to grow cells for long time and potentially employable in the biomedical field., Conclusion: Although these materials are cytotoxic under certain circumstances, we have found a suitable coating and specific experimental conditions that encourage using buckypapers as novel scaffolds for cell growth and for potential applications in tissue repair and regeneration., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Paolini et al.)

At the few-atom-thick limit, transition-metal dichalcogenides (TMDs) exhibit strongly interconnected structural and optoelectronic properties. The possibility to tailor the latter by controlling the former is expected to have a great impact on applied and fundamental research. As shown here, proton irradiation deeply affects the surface morphology of bulk TMD crystals. Protons penetrate the top layer, resulting in the production and progressive accumulation of molecular hydrogen in the first interlayer region. This leads to the blistering of one-monolayer thick domes, which stud the crystal surface and locally turn the dark bulk material into an efficient light emitter. The domes are stable (>2-year lifetime) and robust, and host strong, complex strain fields. Lithographic techniques provide a means to engineer the formation process so that the domes can be produced with well-ordered positions and sizes tunable from the nanometer to the micrometer scale, with important prospects for so far unattainable applications., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypothesis: Sodium Deoxycholate (NaDC) and Phenylalanine (Phe) are important biological hydrogelators. NaDC hydrogels form by lowering the pH or by increasing the ionic strength. Phe gels form from saturated solution by thermal induction and slow kinetics. The resulting gels hold great potential in medicine and biology as drug carriers and models for fundamental self-assembly in pathological conditions. Based on this background it was hypothesized that a Phe substituted NaDC could provide a molecule with expanded gelling ability, merging those of the precursors., Experiments: We coupled both building blocks in a zwitterionic derivative bearing a Phe residue at the C3 carbon of NaDC. The specific zwitterionic structure, the concurrent use of Ca 2+ ions for the carboxyl group coordination and the pH control generate conditions for the formation of hydrogels. The hydrogels were analyzed by combining UV and circular dichroism spectroscopies, rheology, small angle X-ray scattering and atomic force microscopy., Findings: Hydrogel appearance occurs in conditions that are uncovered in the case of the pure Phe and NaDC: self-standing gels form instantaneously at room temperature, in the 10-12 pH range and down to concentration of 0.17 wt%. Both thixotropic and shake resistant gels can form depending on the derivative concentration. The gels show an uncommon thermal stability in the scanned range of 20-60 °C. The reported system concurrently enriches the hydrogelation properties of two relevant building blocks. We anticipate some potential applications of such gels in materials science where coordination of metal ions can be exploited for templating inorganic nanostructures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is a growing interest in therapeutically targeting the inflammatory response that underlies age-related chronic diseases including obesity and type 2 diabetes. Through integrative small RNA sequencing, we show the presence of conserved plant miR159a and miR156c in dried nuts having high complementarity with the mammalian TNF receptor superfamily member 1a (Tnfrsf1a) transcript. We detected both miR159a and miR156c in exosome-like nut nanovesicles (NVs) and demonstrated that such NVs reduce Tnfrsf1a protein and dampen TNF-α signaling pathway in adipocytes. Synthetic single-stranded microRNAs (ss-miRs) modified with 2'- O -methyl group function as miR mimics. In plants, this modification naturally occurs on nearly all small RNAs. 2'- O -methylated ss-miR mimics for miR156c and miR159a decreased Tnfrsf1a protein and inflammatory markers in hypertrophic as well as TNF-α-treated adipocytes and macrophages. miR156c and miR159a mimics effectively suppress inflammation in mice, highlighting a potential role of plant miR-based, single-stranded oligonucleotides in treating inflammatory-associated metabolic diseases., Competing Interests: Competing interestsThe authors declare no competing interests

Preparation and characterization of a pH and thermosensitive linear l,d-octapeptide-poly(dimethylamino ethyl methacrylate) ((l-Val-d-Val) 4 -PDMAEMA) conjugate is reported. The hydrophobic uncharged linear (l-Val-d-Val) 4 octapeptide was designed to self-assemble in nanotubes by exploiting the tubular self-assembling properties of linear peptides with regularly alternating enantiomeric sequences. pH and thermosensitive PDMAEMA was obtained by atom transfer radical polymerization (ATRP). The conjugate was prepared by click-chemistry on the solid phase synthetized peptide. Because of the strong interactions between the peptide moieties, long single channel nanotubes (0.2-1.5 μm) are formed also at acidic pH with the fully charged polymer. At 25 °C and basic pH the size of the nanotubes did not change significantly. In basic conditions and temperature above the PDMAEMA lower critical solution temperature (LCST) a significant increase of the length of the nanotubes up to several micrometers is observed. The size is retained for several days after cooling back to room temperature. Sonication significantly reduces the nanotube length (0.2-0.5 μm) forming low polydisperse nanotubes. The elongation of the nanotubes is fully reversible by restoring acidic pH. This is the first example, to our knowledge, of thermosensitive peptide-polymer single channel nanotubes with length that can be varied from hundreds of nanometers to several micrometers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypothesis: The peculiar swelling behaviour of poly(N-isopropylacrylamide) (PNIPAM) 4 -based responsive microgels provides the possibility to tune both softness and volume fraction with temperature, making these systems of great interest for technological applications and theoretical implications. Their intriguing phase diagram can be even more complex if poly(acrylic acid) (PAAc) 5 is interpenetrated within PNIPAM network to form Interpenetrating Polymer Network (IPN) 6 microgels that exhibit an additional pH-sensitivity. The effect of the PAAc/PNIPAM polymeric ratio on both swelling capability and dynamics is still matter of investigation., Experiments: Here we investigate the role of PAAc in the behaviour of IPN microgels across the volume phase transition through dynamic light scattering (DLS), 7 transmission electron microscopy (TEM) 8 and electrophoretic measurements as a function of microgel concentration and pH., Findings: Our results highlight that aggregation is favored at increasing weight concentration, PAAc content and pH and that a crossover PAAc content C PAAc ∗ 9 exists above which the ionic charges on the microgel become relevant. Moreover we show that the softness of IPN microgels can be tuned ad hoc by changing the PAAc/PNIPAM ratio. These findings provide new insights into the possibility to control experimentally aggregation properties, charge and softness of IPN microgels by varying PAAc content., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The self-aggregation of inherently chiral, (l)-proline functionalised Cu and Zn porphyrin derivatives has been investigated in different aqueous organic solvent media. The results indicate that the title species form self-assembled structures expressing supramolecular chirality by the amplification of the stereochemical information stored on the l-prolinate functionality. A substantial difference of the aggregation modes, and the chiroptical features of the final supramolecular species for the two investigated complexes, is clearly imputable to the metal ions, having a different coordination ability toward solvent molecules. Detailed kinetic investigation performed by combining different spectroscopy techniques allowed the definition of the reaction mechanisms involved in these processes. The results described are of importance, for example, for the achievement of stereoselective devices and sensors.

Hypothesis: Bolaamphiphiles are characterized by wide polymorphism of their aggregates, due to the connection of the headgroups that renders their investigation very intriguing in several technological applications. Some bolaamphiphiles displaying the triphenylphosphonium motif (TPP-bolaamphiphiles) were previously explored for their ability in crossing the mitochondrial membranes but their colloidal features, which are crucial for the potential development of an effective drug delivery system, were never investigated., Experiments: Single chain TPP-bolaamphiphiles, featuring chains of 12, 16, 20 and 30 methylene units, were synthesized and their aggregation features (Krafft point, cac, dimensions, morphology, stability) were investigated by conductivity, dialysis, transmission electron microscopy, Raman spectroscopy, dynamic and dielectrophoretic laser light scattering measurements., Findings: All the TPP-bolaamphiphiles spontaneously self-assemble into vesicles, independently of the chain length. The bolaamphipile with the longest chain forms monodispersed vesicles whereas for the other bolaamphiphiles two distinct populations of vesicles are observed. All vesicles are not equilibrium systems, in particular vesicles formed by the bolaamphiphiles featuring 20 and 30 methylene units result notably stable to dilution thanks to both the tightening of molecular packing at increasing chain length and the progressive reduction of the monomer percentage in U-shaped conformation. These features make these TPP-bolaamphiphiles very attractive as minor components for the development of novel mitochondriotropic liposomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)