Blue-Light-Activated Water-Soluble Sn(IV)-Porphyrins for Antibacterial Photodynamic Therapy (aPDT) against Drug-Resistant Bacterial Pathogens.

Antimicrobial resistance has emerged as a global threat to the treatment of infectious diseases. Antibacterial photodynamic therapy (aPDT) is a promising alternative approach and is highly suitable for the treatment of cutaneous bacterial infections through topical applications. aPDT relies on light-responsive compounds called photosensitizer (PS) dyes, which generate reactive oxygen species (ROS) when induced by light, thereby killing bacterial cells. Despite several previous studies in this area, the molecular details of targeting and cell death mediated by PS dyes are poorly understood. In this study, we further investigate the antibacterial properties of two water-soluble Sn(IV) tetrapyridylporphyrins that were quaternized with methyl and hexyl groups (1 and 2). In this follow-up study, we demonstrate that Sn(IV)-porphyrins can be photoexcited by blue light (a 427 nm LED) and exhibit various levels of bactericidal activity against both Gram-(+) and Gram-(-) strains of bacteria. Using localization studies through fluorescence microscopy, we show that 2 targets the bacterial membrane more effectively than 1 and exhibits comparatively higher aPDT activity. Using multiple fluorescence reporters, we demonstrate that photoactivation of 1 and 2 results in extensive collateral damage to the bacterial cells including DNA cleavage, membrane damage, and delocalization of central systems necessary for bacterial growth and division. In summary, this investigation provides deep insights into the mechanism of bacterial killing mediated by the Sn(IV)-porphyrins. Moreover, our approach offers a new method for evaluating the activity of PS, which may inspire the discovery of new PS with enhanced aPDT activity.

Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment.

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸem). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.

Photodynamic antimicrobial chemotherapy activities of phthalocyanine-antibiotic conjugates against bacterial biofilms and interactions with extracellular polymeric substances.

This study sheds light on how to rationally design efficient photodynamic antimicrobial chemotherapy (PACT) agents by covalently linking phthalocyanines (Pcs) as photosensitizers with an antibiotic: Ciprofloxacin (CIP). Pcs used are zinc (II) 3-(4-((3,17,23-tris(4-(Benzo(d)thiazol-2-yl] thiol) phthalocyanine-9-yl) oxy) phenyl) propanoic acid (1) and zinc (II) 3-(4-(3,17,23-tris(3-(4-(triphenylphosphine) butyl) benzo[d]thiazol-3-ium bromide phthalocyanine-9-yl) oxy) phenyl) propanoic acid (2). High singlet oxygen quantum yields are observed in the presence of CIP. Square wave voltammetry was used to analyse the Pc-CIP uptake by bacteria biofilms of Streptococcus pneumoniae (S. pneumonia) and Escherichia coli (E. coli). Electrochemical impedance spectroscopy and scanning electron spectroscopy were used to study the stability of the biofilms in the presence Pc-CIP complexes and when exposed to light. Raman and time of flight-secondary ion mass spectrometry (TOF-SIMS) are used to identify the breakdown of cellular components of the biofilm and penetration of the Pc-CIP into the biofilms, respectively.

The application of Sn(IV)Cl2 and In(III)Cl porphyrin-dyed TiO2 nanofibers in photodynamic antimicrobial chemotherapy for bacterial inactivation in water.

The World Health Organization has reported that antimicrobial resistance is one of the top 10 health threats that humanity faces today. Due to this, alternative therapies to the common antimicrobials are being explored and among these is photodynamic antimicrobial chemotherapy, where a combination of light, a photosensitizer and reactive oxygen species can be used to target microbial cells. In this research, free base, tin (IV) and indium (III) tetramethoxyporphyrins photosensitizers are adsorbed onto inorganic titanium dioxide nanofibers in an effort to create reusable fibers that are effective against Staphylococcus aureus. The photodynamic antimicrobial chemotherapy studies indicate that the metalloporphyrin adsorbed nanofibers exhibit good photodynamic antimicrobial activity against Staphylococcus aureus where the Cl2Sn(IV) tetramethoxyporphyrin dyed TiO2 exhibited 100% bacterial inhibition after a 30 min irradiation period.

The photodynamic activity properties of a series of structurally analogous tetraarylporphyrin, chlorin and N-confused porphyrin dyes and their Sn(IV) complexes.

A series of tetraarylporphyrin, -chlorin and N-confused porphyrin dyes with 4­methoxy­meso-aryl rings (1-Por, 1-Chl and 1-NCP) and their Sn(IV) complexes (1-SnPor, 1-SnChl and 1-SnNCP) have been synthesized and characterized. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.67, 0.71 and 0.85 for 1-SnPor, 1-SnChl and 1-SnNCP, respectively. The photodynamic activities of 1-Por, 1-Chl, 1-NCP, 1-SnPor, 1-SnChl and 1-SnNCP were determined against MCF-7 breast cancer cells through illumination with Thorlabs 625 or 660 nm (240 or 280 mW.cm-2) light emitting diodes (LEDs) for 20 min. The IC50 values for 1-SnChl and 1-SnNCP lie between 1.4 - 6.1 and 1.6 - 4.8 µM upon photoirradiation with the 660 and 625 nm LEDs, respectively, while higher values of >10 µM were obtained for 1-SnPor and the free base dyes. In a similar manner, 1-SnChl and 1-SnNCP were found to also have significantly higher photodynamic antimicrobial activity against planktonic Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli bacteria than the other dyes studied. Upon illumination with Thorlabs 625 and 660 nm LEDs for 75 min, Log10 reduction values of 7.62 and > 2.40-3.69 were obtained with 1 and 5 µM solutions, respectively.

The development of folate-functionalised palladium nanoparticles for folate receptor targeting in breast cancer cells.

Folate receptor-targeted therapy has excellent prospects for the treatment of breast cancer. A non-toxic concentration of folate-conjugated palladium-based nanoparticles was used to target the overexpressed folate receptor on breast cancer cells. The folate-conjugated nanoparticles were tailored to accumulate selectively in cancer cells relative to normal cells via the folate receptor. The MDA-MB-231, MDA-MB-468, MCF-7 breast cancer cell lines, and MCF-10A normal cell lines were used in the study. Qualitative and quantitative analysis of nanoparticle cellular uptake and accumulation was conducted using transmission electron microscopy and inductively coupled plasma-optical emission spectroscopy. The findings proved that folate-conjugated palladium nanoparticles successfully and preferentially accumulated in breast cancer cells. We conclude that folate-conjugated palladium nanoparticles can be potentially used to target breast cancer cells for radiopharmaceutical applications.

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.

Fibrous TiO2 Alternatives for Semiconductor-Based Catalysts for Photocatalytic Water Remediation Involving Organic Contaminants.

Water decontamination remains a challenge in several developed and developing countries. Affordable and efficient approaches are needed urgently. In this scenario, heterogeneous photocatalysts appear as one of the most promising alternatives. This justifies the extensive attention that semiconductors, such as TiO2, have gained over the last decades. Several studies have evaluated their efficiency for environmental applications; however, most of these tests rely on the use of powder materials that have minimal to no applicability for large-scale applications. In this work, we investigated three fibrous TiO2 photocatalysts, TiO2 nanofibers (TNF), TiO2 on glass wool (TGW), and TiO2 in glass fiber filters (TGF). All materials have macroscopic structures that can be easily separated from solutions or that can work as fixed beds under flow conditions. We evaluated and compared their ability to bleach a surrogate dye molecule, crocin, under batch and flow conditions. Using black light (UVA/visible), our catalysts were able to bleach a minimum of 80% of the dye in batch experiments. Under continuous flow experiments, all catalysts could decrease dye absorption under shorter irradiation times: TGF, TNF, and TGW could, respectively, bleach 15, 18, and 43% of the dye with irradiation times as short as 35 s. Catalyst comparison was based on the selection of physical and chemical criteria relevant for application on water remediation. Their relative performance was ranked and applied in a radar plot. The features evaluated here had two distinct groups, chemical performance, which related to the dye degradation, and mechanical properties, which described their applicability in different systems. This comparative analysis gives insights into the selection of the right flow-compatible photocatalyst for water remediation.

The Photodynamic Anticancer and Antibacterial Activity Properties of a Series of meso-Tetraarylchlorin Dyes and Their Sn(IV) Complexes.

A series of tetraarylchlorins with 3-methoxy-, 4-hydroxy- and 3-methoxy-4-hydroxyphenyl meso-aryl rings (1-3-Chl) and their Sn(IV) complexes (1-3-SnChl) were synthesized and characterized so that their potential utility as photosensitizer dyes for use in photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) can be assessed. The photophysicochemical properties of the dyes were assessed prior to in vitro PDT activity studies against MCF-7 breast cancer cells through irradiation with Thorlabs 625 or 660 nm LED for 20 min (240 or 280 mW·cm-2). PACT activity studies were performed against both planktonic bacteria and biofilms of Gram-(+) S. aureus and Gram-(-) E. coli upon irradiation with Thorlabs 625 and 660 nm LEDs for 75 min. The heavy atom effect of the Sn(IV) ion results in relatively high singlet oxygen quantum yield values of 0.69-0.71 for 1-3-SnChl. Relatively low IC50 values between 1.1-4.1 and 3.8-9.4 µM were obtained for the 1-3-SnChl series with the Thorlabs 660 and 625 nm LEDs, respectively, during the PDT activity studies. 1-3-SnChl were also found to exhibit significant PACT activity against planktonic S. aureus and E. coli with Log10 reduction values of 7.65 and >3.0, respectively. The results demonstrate that the Sn(IV) complexes of tetraarylchlorins merit further in depth study as photosensitizers in biomedical applications.

Sn(IV)-porphyrinoids for photodynamic anticancer and antimicrobial chemotherapy.

Photodynamic therapy (PDT) is a mode of treatment for different types of cancers, which involves a nontoxic photosensitizer (PS), a light source to activate the PS, and ground-state molecular oxygen (3O2). Light activation of the PS leads to the generation of reactive oxygen species (ROS), which initiates a toxic effect on the surrounding cellular substrates, thereby destroying the cancerous cells. The commercially used PDT drug Photofrin® which is a tetrapyrrolic porphyrin-based photosensitizer has drawbacks such as aggregation in water, prolonged skin photosensitivity, variability in chemical compositions, and minimal absorbance in the red-light region. Metallation of the porphyrin core with diamagnetic metal ions aids the photogeneration of singlet oxygen (ROS). Metalating with Sn(IV) provides a six-coordination octahedral geometry with trans-diaxial ligands. This approach suppresses aggregation in aqueous media and increases ROS generation upon light exposure due to the heavy atom effect. Bulky trans-diaxial ligation hinders the approach of the Sn(IV) porphyrins, thereby suppressing aggregation effects. In this review, we document the recently reported Sn(IV) porphyrinoids and their photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity properties. In a similar manner to PDT, the photosensitizer is used to kill the bacteria upon irradiation with light during PACT. Often, bacteria develop resistance against conventional chemotherapeutic drugs over time, decreasing their antibacterial properties. However, in the case of PACT, it is difficult to generate resistance against singlet oxygen produced by the photosensitizer.

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.

Photoantimicrobial activity of Schiff-base morpholino phthalocyanines against drug resistant micro-organisms in their planktonic and biofilm forms.

Antimicrobial photodynamic inactivation (aPDI) is a treatment for the eradication of drug-resistant micro-organisms. One of the advantages of this technique, is that there is minimal possibility of microbial resistance. Hence, herein, the preparation and characterization of novel neutral and cationic morpholine containing Schiff base phthalocyanines are reported. The cationic complexes gave moderate singlet oxygen quantum yields (ΦΔ) of ∼0.2 in aqueous media. Conversely, the neutral complexes generated very low ΦΔ values making them very poor candidates for antimicrobial studies. The cationic phthalocyanines showed excellent photodynamic activity against planktonic cells of all micro-organisms (Candida albicans, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica subspecies enterica serovar Choleraesuis, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus). The efficiency of aPDI was shown to be both concentration and light-dose-dependent. Mono biofilms were susceptible when treated with 200 µM of cationic Pcs at 108 J/cm2. However, ∼10% of the mixed biofilm survived after treatment.

Methylthiophenyl- and Methylthiobiphenyl-Substituted A2B CoIIIcorroles: Modulating Electrocatalyzed Hydrogen Evolution Reactions on Surface-Modified Gold Electrodes.

Four A2B-type CoIIIcorroles (2a-2d) with electron-donating/withdrawing substituents at the A2 meso-aryl substituents and a 4-(methylthio)phenyl ring at the B position have been synthesized and characterized, along with a series of meso-extended CoIIIcorroles (4a-4c) with 4'-(methylthio)biphenyl moieties. The electronic structures and structure-property relationships of the dyes have been analyzed by comparing their redox and optical properties to trends predicted in density functional theory calculations. Au electrodes surface-modified with 2a-2d and 4a-4c are highly efficient catalysts for electrocatalyzed hydrogen evolution reactions, and the electrocatalytic properties can be readily modulated by fine-tuning the electronic structure of the CoIIIcorrole and the distance between the "Au-S" bond and CoIII center.

The in-vitro proliferation-suppression of MCF-7 and HeLa cell lines mediated by differently substituted ionic phthalocyanines in sonodynamic therapy supplemented-photodynamic therapy.

This work focuses on the study of the effects of the ultrasonic frequency (MHz) and power (W.cm-2) on the stability, reactive oxygen species yields and cytotoxicity activities of differently substituted ionic phthalocyanines (Pcs) in sonodynamic therapy (SDT). Four ultrasonic parameters were investigated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). A higher degradation of the Pcs was observed with increasing power at the Par II. Two reactive oxygen species (ROS) were detected in the ultrasound treated Pcs: singlet oxygen and hydroxyl radicals. Due to minimal degradation of most Pcs, Par I was chosen for SDT, photodynamic therapy (PDT), and photo-sonodynamic therapy (PSDT) against Michigan Cancer Foundation-7 and Henrietta Lacks cancer cell lines. PSDT generally showed improved therapeutic efficacies of the Pcs compared to the SDT and PDT mono treatments.

A hypoxia responsive silicon phthalocyanine containing naphthquinone axial ligands for photodynamic therapy activity.

A liposome loaded­silicon (IV) phthalocyanine (SiPc) containing naphthoquinone axial ligands as hypoxia-responsive a prodrug-like moieties (Prodrug-SiPc), is herein reported. With the help of computational methods, this study assessed the photophysical, photochemical and electrochemical redox properties of the Prodrug-SiPc to elucidate the relationship between material structure and properties. The attachment of the axial quinoid moieties endowed the Prodrug-SiPc with Type I/II photochemical and prodrug-like properties. Following liposomal encapsulation, the therapeutic efficacy of Prodrug-SiPc-liposomes was investigated against Michigan Cancer Foundation-7 (MCF-7) and Henrietta Lacks (Hela) cancer cells as in vitro cancer models and revealed that the as-synthesized Prodrug-SiPc-liposomes are potential photodynamic therapy (PDT) drug candidates. The Prodrug-SiPc-liposome takes full advantage of the hypoxic microenvironment of tumors - a side effect PDT - to trigger therapy, resulting in significantly enhanced efficacy compared to typical PDT. This work highlights the importance of multiple characteristics in designing new and effective photosensitizer candidates.

Co phthalocyanine mediated electrochemical detection of the HER2 in the presence of Au and CeO2 nanoparticles and graphene quantum dots.

In this work, cobalt tetra phenoxy acetic acid phthalocyanine (CoTAPc) is investigated as an electron mediator, immobilization platform for an HB5 aptamer and to enhance the electrochemical signal for the detection of human epidermal growth factor receptor 2 (HER2). Furthermore, the CoTAPc was combined individually with sulphur/nitrogen doped graphene quantum dots (SNGQDs), gold nanoparticles (AuNPs) and cerium oxide nanoparticles (CeO2NPs), on a glassy carbon electrode (GCE) via sequential adsorption. The CoTAPc and SNGQDs were also π-π stacked, used for electrode modification similarly to the rest of the other surfaces and applied towards the electrochemical detection of HER2. The designed sensors were characterized using electrochemical impedance spectroscopy (EIS). The designed aptasensors showed detection limits as low as 6.0 pg/mL. The real life applicability of the designed aptasensors was tested in human serum samples. The aptasensors showed great storage stability, sensitivity and specificity towards HER2, implying great potential for applications in early diagnosis of breast cancer.

Diiodinated Mono- and Dipyridylvinyl BODIPY Dyes: Photophysicochemical Properties, in vitro Antibacterial Studies, Molecular Docking and Theoretical Calculations.

In this study, novel mono- and dipyridylvinyl boron dipyrromethene dyes are prepared to compare their photodynamic antimicrobial chemotherapy (PACT) activities against Staphylococcus aureus to the corresponding core dyes. Pyridylvinyl substitution at the 3- or 3,5-positions of a meso-4-bromophenylBODIPY core dye via a Knoevenagel reaction with an aromatic 2-bromopyridinecarboxaldehyde shifts the major BODIPY spectral band to longer wavelength. The extended π-conjugation red shifts the main spectral band into the 602-618 nm region in CHCl3 , THF, ethanol and DMSO after monopyridylvinyl substitution and to 685-704 nm after dipyridylvinyl substitution. An enhancement of the population of the T1 state through the incorporation of iodine atoms at the 2,6-positions results in moderately high singlet oxygen quantum yields in DMSO. The π-extended dyes were found to have significantly lower PACT activities than the diiodinated core dye.

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.

Photodynamic antimicrobial chemotherapy with asymmetrical cationic or neutral metallophthalocyanines conjugated to amino-functionalized zinc oxide nanoparticles (spherical or pyramidal) against planktonic and biofilm microbial cultures.

The synthesis and characterization of neutral zinc and indium substituted mercaptobenzothiazole substituted phthalocyanines (Pcs) and their respective cationic derivatives are presented. The phthalocyanines were further covalently linked to two differently shaped amino-functionalized ZnO nanoparticles (ZnONPs): namely nanospheres (NH2-ZnONSp), and nanopyramids (NH2-ZnONPy), to form corresponding nanoconjugates. The photophysicochemical properties of each nanocomposite were determined, and the Pc-ZnONPs produced high singlet oxygen quantum yields. The photodynamic antimicrobial chemotherapy activity was determined using planktonic and biofilm cells of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Candida albicans (C. albicans). The conjugates of the cationic Pc derivatives with ZnONPy produced the highest log reduction values (∼ 8 and above) with the complete elimination of all planktonic cells at 0.45 kJ/cm2 for S. aureus and at 0.9 kJ/cm2 for E. coli, and C. albicans. For biofilms log reduction values >3 for both S. aureus and E. coli were obtained. The conjugates of the cationic Pc derivatives with NH2-ZnONPy showed great potential in eradicating mixed microbial biofilms.