A search for enhanced photodynamic activity against Staphylococcus aureus planktonic cells and biofilms: the evaluation of phthalocyanine-detonation nanodiamond-Ag nanoconjugates.

The present work reports on the synthesis and characterization of novel zinc (2) and indium (3) 2-amino-4-bromophenoxy substituted phthalocyanines (Pcs) along with the self-assembled nanoconjugates formed viaπ-π stacking interaction onto detonation nanodiamonds (DNDs) to form 2@DNDs and 3@DNDs. 2@DNDs and 3@DNDs were covalently linked to chitosan-silver mediated nanoparticles (CSAg) to form 2@DNDs-CSAg and 3@DNDs-CSAg nanoconjugates. High singlet oxygen quantum yields in DMSO of 0.69 and 0.72 for Pcs alone and 0.90 and 0.92 for 2@DNDs-CSAg and 3@DNDs-CSAg, respectively, were obtained. The photodynamic antimicrobial chemotherapy (PACT) activity of both phthalocyanines and nanoconjugates was tested against planktonic cells and biofilms of S. aureus. 2@DNDs-CSAg and 3@DNDs-CSAg caused effective killing with a log reduction of 9.74. In addition, PACT studies on single-species S. aureus biofilms were carried out with log reduction values of 5.12 and 5.27 at 200 µg mL-1 for 2@DNDs-CSAg and 3@DNDs-CSAg, respectively.

Combination of photodynamic antimicrobial chemotherapy and ciprofloxacin to combat S. aureus and E. coli resistant biofilms.

Photodynamic antimicrobial chemotherapy (PACT) coupled with an antibiotic, ciprofloxacin (CIP), was investigated using two indium metallated cationic photosensitizers, a porphyrin (1) and a phthalocyanine (2). Applying PACT followed by the antibiotic treatment led to a remarkable reduction in the biofilm cell survival of two antibiotic-resistant bacterial strains, S. aureus (Gram-positive) and E. coli (Gram-nenative). Treating both bacteria strains with PACT alone showed no significant activity at 32 µM with 15 min irradiation, while CIP alone exhibited a minimum biofilm inhibition concentration (MBIC) at 4 and 8 µg/mL on S. aureus and E. coli, respectively following 24 h incubation. The combined treatment resulted in the complete eradication of the matured biofilms with high log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively, at low concentrations. It was found that 15 min PACT irradiation of 8 µM of complexes (1 and 2) combined with 2 µg/mL of CIP have a 100% reduction of the resistant S. aureus biofilms. Whereas the total killing of E. coli was obtained when combining 8 µM of complex 1 and 16 µM of complex 2 both combined with 4 µg/mL of CIP.

Single vs sandwich aptamers: Towards the detection of human epidermal growth factor receptor 2 using composites of phthalocyanine and nanoparticles.

The superiority of the sandwich over a single aptamer based aptasensor assay for the detection of the human epidermal growth factor receptor 2 (HER2) is demonstrated for the first time. Cobalt tris-3,5 dimethoxy-phenoxy pyridine (5) oxy (2)- carboxylic acid phthalocyanine (CoMPhPyCPc) and sulphur/nitrogen doped graphene quantum dots (SNGQDs) and cerium oxide nanoparticles (CeO2NPs) nanocomposite (SNGQDs@CeO2NPs) were used for electrode modification of glassy carbon electrode (GCE) both individually and combined to form the substrates: GCE/SNGQDs@CeO2NPs, GCE/CoMPhPyCPc and GCE/SNGQDs@CeO2NPs/CoMPhPyCPc. The designed substrates were used as immobilization platforms for the amino functionalized HB5 aptamer for the development of both single and sandwich aptasensor assays. A novel bioconjugate, made of the HB5 aptamer and nanocomposite (HB5-SNGQDs@CeO2NPs) was fabricated, and characterized using ultra-violet/visible, Fourier transform infrared, and Raman spectroscopies as well as scanning electron microscopy. HB5-SNGQDs@CeO2NPs was applied as a secondary aptamer in the design of novel sandwich assays towards the electrochemical detection of HER2. The performance of the designed aptasensors were evaluated using electrochemical impedance spectroscopy. The sandwich assay gave low limit of detection of 0.00088 pg/mL, high sensitivity of 773925 Ω pg-1mL, showed stability, and good precision in real samples towards HER2 detection.

Evaluation of the antibacterial activity of gallic acid anchored phthalocyanine-doped silica nanoparticles towards Escherichia coli and Staphylococcus aureus biofilms and planktonic cells.

In this work, we have described the synthesis of phthalocyanine complexes Zn(II) tetrakis 4-(5-formylpyridin-2-yl)oxy) phthalocyanine (2), Zn(II) tetrakis-1­butyl­4-(2-(6- (tetra-phenoxy)pyridin-3-yl) vinyl)pyridin-1-ium phthalocyanine (3) and Zn(II) tetrakis 1­butyl­5-(2-(1-butylpyridin-1-ium-4-yl)vinyl)-2-(tetra-phenoxy)pyridin-1-ium phthalocyanine (4). The effect of a varying number of charges when the Pc complexes are alone or grafted in gallic acid (GA) tagged silica nanoparticles on photodynamic antimicrobial chemotherapy (PACT) is investigated toward Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli) in both planktonic and biofilm forms. Complex 4, bearing a total of 8 cationic charges, displayed the highest activity with log CFU (colony forming units) values of 8.60 and 6.42 against E.coli and S.aureus biofilms, respectively. The surface stability of E.coli and S.aureus biofilms in the presence of 4 and its conjugate was analyzed using cyclic voltammetry. Scanning electron microscopy (SEM) and Raman spectra are also used to study the conformational and biochemical changes within biofilm upon subjecting them to PACT.

The implications of ortho-, meta- and para- directors on the in-vitro photodynamic antimicrobial chemotherapy activity of cationic pyridyl-dihydrothiazole phthalocyanines.

Cationic Zn phthalocyanine complexes were derived by alkylation reaction of tetra-(pyridinyloxy) phthalocyanines (Pcs) at the ortho, meta, and para positions to form Zn (II) tetrakis 3-(4-(2-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (2), Zn (II) tetrakis 3-(4-(3-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (4) and Zn (II) tetrakis 3-(4-(4-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (6). The photophysicochemical behaviors of the Pc complexes were assessed. The meta and para-substituted complexes gave high singlet oxygen quantum yields. The cationic Pcs demonstrated good planktonic antibacterial activity against Staphylococcus aureus and Escherichia coli with the high log reduction values of 9.29 and 8.55, respectively. The cationic complexes also showed a significant decrease in the viability of in vitro biofilms after photo-antimicrobial chemotherapy at 100 µM for both Staphylococcus aureus and Escherichia coli biofilms.

Novel cationic-chalcone phthalocyanines for photodynamic therapy eradication of S. aureus and E. coli bacterial biofilms and MCF-7 breast cancer.

New tetrasubstituted zinc (II) and indium (III) phthalocyanines bearing dimethylamino chalcone group (complexes 3 and 4) as well as their quaternized analogs (3a and 4a) have been assessed for their photodynamic therapy (PDT) of cancer as well as photodynamic antimicrobial chemotherapy activities against biofilms and planktonic cultures of pathogenic bacteria of Staphylococcus aureus and Escherichia coli. Compared to the non-quaternized phthalocyanines 3 and 4, the cationic phthalocyanines 3a and 4a exhibit a higher photodynamic inactivation against the planktonic cells with log reduction values above 9 at a concentration of 1.25 µM. This was attributed to the positive charge which enhances cellular uptake. More interestingly, 3a and 4a show a higher photodynamic inactivation (less than 3% of S. aureus survived) on their biofilm counterparts thanks to their stronger affinity to these cells. 3a and 4a Pcs also exhibited interesting PDT activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 µM, respectively following 15 min irradiation. The obtained results in this work show that the positively charged phthalocyanines 3a and 4a are potential antibacterial photosensitizers that show some selectivity toward the Gram-positive and Gram-negative bacteria as well as MCF-7 breasts cancer cells.

Photodynamic Antimicrobial Action of Asymmetrical Porphyrins Functionalized Silver-Detonation Nanodiamonds Nanoplatforms for the Suppression of Staphylococcus aureus Planktonic Cells and Biofilms.

New asymmetrical porphyrin derivatives containing a p-hydroxyphenyl moiety and p-acetylphenyl moieties along with their functionalized silver-detonation nanodiamonds nanohybrids were characterized and their photophysicochemical properties were established. The study provides evidence that the metalated porphyrin derivatives were red-shifted in absorption wavelength and possessed high singlet oxygen quantum yield comparative to the unmetalated core, thus making them suitable agents for photodynamic antimicrobial chemotherapy. As a result of conjugation to detonation nanodiamonds and silver nanoparticles, these compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant S. aureus strain due to synergetic effect, compared to Ps alone. This suggests that the newly prepared nanohybrids could be used as a potential antimicrobial agent in the treatment of biofilms caused by S. aureus strain.

Synergistic anti-inflammatory activities of a new flavone and other flavonoids from Tephrosia hildebrandtii vatke.

A new flavone, named hildeflavone (1) along with 7 other known flavonoids were isolated from the aerial parts of Tephrosia hildebrandtii Vatke. Their characterisation was based on NMR and MS data analysis. The anti-inflammatory properties of the crude extract, isolated compounds and combination of the compounds were investigated in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Treatment of the LPS-stimulated PBMCs with the isolated flavonoids at a concentration of 100 µM significantly reduced the production of interleukins (IL-1ß, IL-2 and IL-6), interferon-gamma (IFN-γ), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-α). It was also found that the combination of a flavone and flavanones exhibited remarkable synergistic anti-inflammatory effects on the production of the cytokines.[Figure: see text].

Detonation nanodiamonds-phthalocyanine photosensitizers with enhanced photophysicochemical properties and effective photoantibacterial activity.

The nanophotosensitizers based on acetophenoxy tetrasubstituted metallophthalocyanines (MPc) and detonation nanodiamonds (DNDs) were successfully formed and their photophysicochemical properties were determined. The zinc(II)Pc and indium(III)Pc complexes along with their nanoconjugates were found to have high singlet oxygen quantum yields (0.72 - 0.84) associated with the heavy central metal effect. The ability of the functional groups present on the DNDs to bind to the bacteria cell and the improved solubility of the nanoconjugates due to DNDs resulted in effective photodynamic antimicrobial therapy (PACT) activity against S. aureus planktonic cells, with the highest log reduction of 9.72 ± 0.02 for the conjugate of InPc conjugate with DNDs after 30 min irradiation. PACT studies were investigated at a dose of 10 µg/mL for each sample. The results suggest that the readily synthesized nanoconjugates can be used as appropriate PACT agents.

Acetophenone substituted phthalocyanines and their graphene quantum dots conjugates as photosensitizers for photodynamic antimicrobial chemotherapy against Staphylococcus aureus.

This work reports on the synthesis and characterization of novel acetophenone substituted phthalocyanines along with the self-assembled nanoconjugates formed via π-π stacking interaction between the synthesized unmetalated (2), zinc (3) and indium (4) phthalocyanines and graphene quantum dots (GQDs) to form 2@GQDs, 3@GQDs and 4@GQDs. The complexes and conjugates exhibited high singlet oxygen ranging from 0.20 to 0.79 in DMSO for Pcs and nanoconjugates where in all cases, the indium complexes showed the highest singlet oxygen quantum yields. The photodynamic antimicrobial chemotherapy activity of both phthalocyanines and nanoconjugates were tested against Staphylococcus aureus. 4@GQDs was found to be highly effective causing a 9.68 log reduction of the bacteria at 10 µM (based on Pc) when compared to 3.77 log reduction of 3@GQDs.