Nanoarchitectonics of Electrically Activable Phosphonium Self-Assembled Monolayers to Efficiently Kill and Tackle Bacterial Infections on Demand.

Prosthetic implants are widely used in dentistry and orthopedics and, as a result, infections can occur which cause their removal. Therefore, it is essential to propose methods of eradicating the bacteria that remain on the prosthesis during treatment. For this purpose, it is necessary to develop surfaces whose antibacterial activity can be controlled. Herein, we designed innovative and smart phosphonium self-assembled monolayer (SAM) interfaces that can be electrically activated on demand for controlling bacterial contaminations on solid surfaces. Upon electroactivation with a low potential (0.2 V for 60 min., conditions determined through a DOE), a successful stamping out of Gram-positive and Gram-negative bacterial strains was obtained with SAM-modified titanium surfaces, effectively killing 95% of Staphylococcus aureus and 90% Klebsiellapneumoniae. More importantly, no toxicity towards eukaryotic cells was observed which further enhances the biocompatible character of these novel surfaces for further implementation.

Nucleoside-Lipid-Based Nanoparticles for Phenazine Delivery: A New Therapeutic Strategy to Disrupt Hsp27-eIF4E Interaction in Castration Resistant Prostate Cancer.

Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5'-(2',3'-dioleoyl)uridine]-N',N',N'-trimethylammonium tosylate) and DOU-PEG2000 (5'-PEG2000-2',3'-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy.

Phosphonium-ammonium-based di-cationic ionic liquids as antibacterial over the ESKAPE group.

Emergence of antibioresistance is currently a major threat of public health worldwide. Hence there is an urge need of finding new antibacterial material. Herein, we report a simple and eco-friendly method to synthesize homo and heterodicationic ionic liquids based on quaternary phosphonium and ammonium salt. In order to investigate the structure activity relationship (SAR) we measured the MICs of a series of 16 derivatives with structural variations (nature of cations and counter-ions, size of linker and alkyl side chains as well as structural symmetry) over a range of Gram-positive and Gram-negative bacterial strains from the ESKAPE group. Some of the tested structures exhibit high antimicrobial activities (MIC = 0.5 mg/L) and are active over a wide range of bacteria from Gram-positive to Gram-negative. Overall, these results reveal the strong potential of di-cationic derivatives as antibacterial agents and the determination of activities from structural features gives decisive information for future synthesis of such di-cationic structures for biocidal purpose.

Recent Electrochemical/Electrical Microfabricated Sensor Devices for Ionic and Polyionic Analytes.

The recent technological advances combined with the development of new concepts and strategies have revolutionized the field of sensor devices, allowing access to increasingly sophisticated device structures associated with high sensitivities and selectivities. Among them, electrochemical and electrical sensors have gained the most interest because they offer unique intrinsic characteristics and meet the requirements to be integrated in more sophisticated devices including microfluidics or lab-on-chips, opening access to multiplex and all-in-one detection devices. In the present article, we outline and provide a short and concise overview on the most recent achievements in the field of electrical detection of ionic species as they display versatile roles in many important biological events and are ubiquitous in environment.

Antibacterial activities of mono-, di- and tri-substituted triphenylamine-based phosphonium ionic liquids.

We report the synthesis of new mono, di and tri phosphonium ionic liquids and the evaluation of their antibacterial activities on both Gram-positive and Gram-negative bacteria from the ESKAPE-group. Among the molecules synthesized some of them reveal a strong bactericidal activity (MIC = 0.5 mg/L) for Gram-positive bacteria (including resistant strains) comparable to that of standard antibiotics. A comparative Gram positive and Gram negative antibacterial activities shows that the nature of counter-ion has no significant effects. Interestingly, the increase of phosphonium lateral chains (from 4 to 8 carbons) results in a decrease of antibacterial activities. However, the increase of the spacer length has a positive influence on the activity on both Gram-positive and Gram-negative bacteria except for E. aerogenes. Finally, the increased charge density has no effect on the Gram-positive antibacterial activities (MIC between 2 and 4 mg/L) but seems to attenuate (except for P. aeruginosa) the discrimination between Gram-positive and Gram-negative. Overall these results suggest a unique mechanism of action of these triphenylamine-phosphonium ionic liquid derivatives.

Antibacterial activities of fluorescent nano assembled triphenylamine phosphonium ionic liquids.

Staphylococcus aureus, a Gram positive coccal bacterium is a major cause of nosocomial infection. We report the synthesis of new triphenylamine phosphonium ionic liquids which are able to self-assemble into multiwall nanoassemblies and to reveal a strong bactericidal activity (MIC=0.5mg/L) for Gram positive bacteria (including resistant strains) comparable to that of standard antibiotics. Time kill, metabolism and fluorescence confocal microscopy studies show a quasi-instantaneously penetration of the nanoassemblies inside the bacteria resulting of a rapid blocking (30min) of their proliferation. As confirmed by rezasurin reduction monitoring, these compounds strongly affect the bacterial metabolism and a Gram positive versus Gram negative selectivity is clearly observed. These fluorescent phosphonium ionic liquid might constitute a useful tool for both translocation studies and to tackle infectious diseases related to the field of implantology.