Dark Antibacterial Activity of Rose Bengal.

The global spread of bacterial resistance to antibiotics promotes a search for alternative approaches to eradication of pathogenic bacteria. One alternative is using photosensitizers for inhibition of Gram-positive and Gram-negative bacteria under illumination. Due to low penetration of visible light into tissues, applications of photosensitizers are currently limited to treatment of superficial local infections. Excitation of photosensitizers in the dark can be applied to overcome this problem. In the present work, dark antibacterial activity of the photosensitizer Rose Bengal alone and in combination with antibiotics was studied. The minimum inhibitory concentrations (MIC) value of Rose Bengal against S. aureus dropped in the presence of sub-MIC concentrations of ciprofloxacin, levofloxacin, methicillin, and gentamicin. Free Rose Bengal at sub-MIC concentrations can be excited in the dark by ultrasound at 38 kHz. Rose Bengal immobilized onto silicon showed good antibacterial activity in the dark under ultrasonic activation, probably because of Rose Bengal leaching from the polymer during the treatment. Exposure of bacteria to Rose Bengal in the dark under irradiation by electromagnetic radio frequency waves in the 9 to 12 GHz range caused a decrease in the bacterial concentration, presumably due to resonant absorption of electromagnetic energy, its transformation into heat and subsequent excitation of Rose Bengal.

Data on peptidyl platform-based anticancer drug synthesis and triton-x-based micellar clusters (MCs) self-assembly peculiarities for enhanced solubilization, encapsulation of hydrophobic compounds and their interaction with HeLa cells.

The data presented here refer to a research article entitled "Self-Assembled Micellar Clusters Based on Triton-X-family Surfactants for Enhanced Solubilization, Encapsulation, Proteins Permeability Control, and Anticancer Drug Delivery" Solomonov et al., 2019. The present article provides the General Procedure for clusterization of Triton-X-based micelles and the effect of (i) metal ion, surfactant, and chelator concentration on the developed clusters formation, (ii) surfactant-chelator relation change, (iii) metal ion-micelles concertation ratio variation, (iv) metal ion replacement, (v) solvent replacement, (vi) kinetics of clusters formation, (vii) hydrophobic fluorescent dye (Coumarin 6) solubilization in aqueous MCs media, (viii) novel anticancer peptidyl drug synthesis and characterization and (ix) the viability of HeLa cells with and without the presence of drug-free Triton-X-based family MCs. These data provide additional insights useful for understanding all aspects of the micellar clusters formation, optimization, and control.

Self-assembled micellar clusters based on Triton-X-family surfactants for enhanced solubilization, encapsulation, proteins permeability control, and anticancer drug delivery.

Non-ionic surfactants have raised a considerable interest for solubilization, encapsulation, permeabilization and controlled release of various compounds due to their unique physicochemical properties. Nevertheless, it is still challenging to create convenient self-assembled multifunctional materials with high solubilization and encapsulation capacities by preserving their advanced capabilities to protect loaded cargos without altering their characteristics. In this work, we present an extended concept of micellar clusters (MCs) formation based on partial entrapment and stabilization of chelate ligands by hydrophobic forces found on the non-ionic surfactant micelle interface of the Triton-X family (TX-100/TX-114), followed by subsequent complexation of the preformed structures either by metal ions or a supporting chelator. The formation aspects, inner structure and the role of external factors such as the addition of competitive ligands have been extensively studied. MCs loaded by hydrophobic fluorescent compounds with high encapsulation efficiency demonstrate an excellent optical response in aqueous media without crystallization as well as sufficient increase in solubility of toxic hydrophobic compounds such as bilirubin (>50 times compared to pure surfactants). Furthermore, Triton-X-based MCs provide a unique feature of selective permeability to hydrophilic ligand-switching proteins such as UnaG and BSA demonstrating bright "turn-on" fluorescence signal either inside the cluster or on its interface via complexation. The proposed strategies allowed us to successfully encapsulate and visualize a newly synthesized, highly hydrophobic anticancer PTR-58-CLB-CAMP peptide drug, while MCs loaded by the drug exhibit a considerable antitumor activity against HeLa cells.

Biolabile peptidyl delivery systems toward sequential drug release.

Compact carriers for peptidyl delivery systems (PDSs) loaded with various drugs were synthesized using a simple and convenient solid phase organic synthesis strategy, including semi-orthogonal functional group protection schemes. Each attachment point of the compact carrier can thus be bound to an anticancer agent through a biodegradable covalent link. Chemo- and biostability experiments of a model peptidyl platform loaded with three different drugs revealed pH and liver homogenate (metabolic) dependent sequential release behavior. The versatility of this approach will serve to expedite the preparation of PDS libraries. This approach may prove useful for applications suitable for personalized medicine where multiple drug delivery is required in a sequential and controlled fashion.

Synthesis, drug release, and biological evaluation of new anticancer drug-bioconjugates containing somatostatin backbone cyclic analog as a targeting moiety.

Peptide conjugates containing somatostatin (SST) cyclic analogs as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing SST receptors (SSTRs), and hence increasing their local efficacy while limiting the peripheral toxicity. Here, we report on the synthesis and biochemical characterization of new SSTR-specific anticancer peptide conjugates, with different anticancer payloads acting through different oncogenic mechanisms to evaluate their biological activities and to provide a comparative study of their drug release profiles. The SSTR2-specific backbone cyclic peptide 3207-86 was chosen for the synthesis of a variety of novel anticancer drug conjugates with a broad drug release capabilities. The N-terminus of 3207-86 was equipped with GABA to generate free amino group available for the conjugation of chlorambucil, Camptothecin (CPT), Combretastatin 4A, ABT-751, and Amonafide through the formation of various biodegradable bonds. The chemo- and biostability/drug release of all the synthetic compounds was investigated at various pHs and in the presence of mouse liver homogenate, respectively. Their selective cytotoxic effect was evaluated on several human cancer cell lines that overexpress SSTR2. Compared with the free drugs, our peptide-drug conjugates exhibited considerable cytotoxic effect on cancer cell lines versus low SSTR2-expressed human embryonic kidney cells. Functional versatility of the conjugates was reflected in the variability of their drug release profiles, whereas the conserved sequence of a selective binding to the SSTR2 likely preserved their binding to the receptor and consequently their favorable toxicity toward targeted cancer cells.

"Switch off/switch on" regulation of drug cytotoxicity by conjugation to a cell targeting peptide.

Bi-nuclear amino acid platforms loaded with various drugs for conjugation to a peptide carrier were synthesized using simple and convenient orthogonally protective solid-phase organic synthesis (SPOS). Each arm of the platform carries a different anticancer agent linked through the same or different functional group, providing discrete chemo- and bio-release profiles for each drug, and also enabling "switch off/switch on" regulation of drug cytotoxicity by conjugation to the platform and to a cell targeting peptide. The versatility of this approach enables efficient production of drug-loaded platforms and determination of favorable drug combinations/modes of linkage for subsequent conjugation to a carrier moiety for targeted cancer cell therapy. The results presented here potentiate the application of amino acid platforms for targeted drug delivery (TDD).