New functionalities were added to biocompatible polycaprolactone nanofiber materials through the co-encapsulation of chlorin e6 trimethyl ester (Ce6) photogenerating singlet oxygen and absorbing light both in the blue and red regions, and using 4-(N-(aminopropyl)-3-(trifluoromethyl)-4-nitrobenzenamine)-7-nitrobenzofurazan, NO-photodonor (NOP), absorbing light in the blue region of visible light. Time-resolved and steady-state luminescence, as well as absorption spectroscopy, were used to monitor both photoactive compounds. The nanofiber material exhibited photogeneration of antibacterial species, specifically nitric oxide and singlet oxygen, upon visible light excitation. This process resulted in the efficient photodynamic inactivation of E. coli not only close to nanofiber material surfaces due to short-lived singlet oxygen, but even at longer distances due to diffusion of longer-lived nitric oxide. Interestingly, nitric oxide was also formed by processes involving photosensitization of Ce6 during irradiation by red light. This is promising for numerous applications, especially in the biomedical field, where strictly local photogeneration of NO and its therapeutic benefits can be applied using excitation in the "human body phototherapeutic window" (600-850 nm). Generally, due to the high permeability of red light, the photogeneration of NO can be achieved in any aqueous environment where direct excitation of NOP to its absorbance in the blue region is limited.

• Klíčová slova
• Antibacterial properties, Nanofibers, Nitric oxide, Polycaprolactone, Red light, Singlet oxygen,
• MeSH
• antibakteriální látky * chemie   farmakologie   MeSH
• chlorofylidy MeSH
• Escherichia coli * účinky léků   účinky záření   MeSH
• fotosenzibilizující látky chemie   farmakologie   MeSH
• nanovlákna * chemie   MeSH
• oxid dusnatý * chemie   metabolismus   MeSH
• polyestery chemie   MeSH
• porfyriny * chemie   farmakologie   MeSH
• singletový kyslík * chemie   metabolismus   MeSH
• světlo * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• chlorofylidy MeSH
• fotosenzibilizující látky MeSH
• oxid dusnatý * MeSH
• phytochlorin MeSH Prohlížeč
• polycaprolactone MeSH Prohlížeč
• polyestery MeSH
• porfyriny * MeSH
• singletový kyslík * MeSH

Tick-borne encephalitis virus (TBEV), the causative agent of tick-borne encephalitis (TBE), is a medically important flavivirus endemic to the European-Asian continent. Although more than 12,000 clinical cases are reported annually worldwide, there is no anti-TBEV therapy available to treat patients with TBE. Porphyrins are macrocyclic molecules consisting of a planar tetrapyrrolic ring that can coordinate a metal cation. In this study, we investigated the cytotoxicity and anti-TBEV activity of a large series of alkyl- or (het)aryl-substituted porphyrins, metalloporphyrins, and chlorins and characterized their molecular interactions with the viral envelope in detail. Our structure-activity relationship study showed that the tetrapyrrole ring is an essential structural element for anti-TBEV activity, but that the presence of different structurally distinct side chains with different lengths, charges, and rigidity or metal cation coordination can significantly alter the antiviral potency of porphyrin scaffolds. Porphyrins were demonstrated to interact with the TBEV lipid membrane and envelope protein E, disrupt the TBEV envelope and inhibit the TBEV entry/fusion machinery. The crucial mechanism of the anti-TBEV activity of porphyrins is based on photosensitization and the formation of highly reactive singlet oxygen. In addition to blocking viral entry and fusion, porphyrins were also observed to interact with RNA oligonucleotides derived from TBEV genomic RNA, indicating that these compounds could target multiple viral/cellular structures. Furthermore, immunization of mice with porphyrin-inactivated TBEV resulted in the formation of TBEV-neutralizing antibodies and protected the mice from TBEV infection. Porphyrins can thus be used to inactivate TBEV while retaining the immunogenic properties of the virus and could be useful for producing new inactivated TBEV vaccines.

• Klíčová slova
• Photosensitization, Porphyrin, Singlet oxygen, Tick-borne encephalitis virus, Viral envelope, Virus-cell fusion,
• MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• internalizace viru MeSH
• kationty terapeutické užití   MeSH
• klíšťová encefalitida * MeSH
• lidé MeSH
• myši MeSH
• porfyriny * farmakologie   terapeutické užití   MeSH
• protilátky virové terapeutické užití   MeSH
• RNA MeSH
• virový obal MeSH
• viry klíšťové encefalitidy * genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• kationty MeSH
• porfyriny * MeSH
• protilátky virové MeSH
• RNA MeSH

The strong antifungal effect of sulfonated polystyrene nanoparticles (NPs) with an encapsulated tetraphenylporphyrin (TPP) photosensitizer is reported here. TPP is activated by visible light, resulting in the generation of singlet oxygen. Its antifungal action is potentiated in the presence of potassium iodide, yielding I2/I3⁻, another antifungal species. The NPs exhibit no dark toxicity, but a broad spectrum of antifungal photodynamic effects. The efficiency of this rapid killing (on the order of minutes) depends on the concentration of TPP NPs, potassium iodide, yeast species and temperature. A strong antifungal activity of TPP NPs is demonstrated on eleven pathogenic and opportunistic pathogenic yeast species (six Candida species and other yeast species, including melanized Hortaea werneckii). The composition and architecture of yeast cell envelope structures clearly influence the efficacy of photodynamic therapy. Candida krusei is the most sensitive to photodynamic therapy. Despite expectations, melanin does not provide Hortaea cells with marked resistance compared to white yeast species. The kinetics of the interaction of NPs with yeast cells is also described. This study may inspire and promote the fabrication of a new type of antiseptic for various skin injuries in clinical medicine.

• Klíčová slova
• Candida, Nanoparticles, Photodynamic therapy, Porphyrin, Singlet oxygen, Yeast,
• MeSH
• antifungální látky farmakologie   terapeutické užití   MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky farmakologie   chemie   terapeutické užití   MeSH
• jodid draselný chemie   farmakologie   MeSH
• nanočástice * chemie   MeSH
• porfyriny * farmakologie   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky MeSH
• fotosenzibilizující látky MeSH
• jodid draselný MeSH
• porfyriny * MeSH

Combating biofilm infections remains a challenge due to the shield and acidic conditions. Herein, an acid-responsive nanoporphyrin (PN3-NP) based on the self-assembly of a water-soluble porphyrin derivative (PN3) is constructed. Additional kinetic control sites formed by the conjugation of the spermine molecules to a porphyrin macrocycle make PN3 self-assemble into stable nanoparticles (PN3-NP) in the physiological environment. Noteworthily, near-infrared (NIR) fluorescence monitoring and synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) effects of PN3-NP can be triggered by the acidity in biofilms, accompanied by intelligent transformation into dot-like nanospheres. Thus, damage to normal tissue is effectively avoided and accurate diagnosis and treatment of biofilms is achieved successfully. The good results of fluorescence imaging-guided photo-ablation of antibiotic-resistant strains methicillin-resistant Staphylococcus aureus (MRSA) biofilms verify that PN3-NP is a promising alternative to antibiotics. Meanwhile, this strategy also opens new horizons to engineer smart nano-photosensitizer for accurate diagnosis and treatment of biofilms.

• Klíčová slova
• MRSA biofilms, NIR fluorescence, acid-responsive nanoporphyrin, phototherapy, structural evolution,
• MeSH
• antibakteriální látky farmakologie   MeSH
• biofilmy MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky farmakologie   MeSH
• fototerapie metody   MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• porfyriny * farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• fotosenzibilizující látky MeSH
• porfyriny * MeSH

Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time.

• Klíčová slova
• cancer, nanoparticles, photodynamic effect,
• MeSH
• buňky NIH 3T3 MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice * MeSH
• porfyriny * metabolismus   farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fotosenzibilizující látky MeSH
• porfyriny * MeSH
• reaktivní formy kyslíku MeSH

Photodynamic therapy (PDT) is one of the treatments for cancer. This therapy uses a combination of a photosensitizer (PS), light irradiation, and oxygen O2, which is converted to cytotoxic 1O2 and other forms of reactive oxygen species (ROS), causing selective damage to the target tissue. In this work, we studied effect of two porphyrin photosensitizers TMPyP and ZnTPPS4 at three different concentrations (0.25, 0.5, 5μM) after two irradiation doses (5 and 25 J/cm2). Photodynamic efect of TMPyP and ZnTPPS4 were confirmed by a battery of in vitro tests including MTT, reactive oxygen species (ROS) production and mitochondrial membrane potential test (MMP). Morphological changes of the cells before and after treatment were imaged by atomic force microscopy (AFM). The most effective combination of irradiation dose and concentration for both PSs showed a concentration of 5 μM and a irradiation dose of 25 J/cm2 in both cell cultures.

• Klíčová slova
• Cancer cells, PDT, Photodynamic therapy, Porphyrine photosensitizer, TMPyP, ZnTPPS(4),
• MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky farmakologie   terapeutické užití   MeSH
• metaloporfyriny * MeSH
• nádory * farmakoterapie   MeSH
• porfyriny * farmakologie   MeSH
• reaktivní formy kyslíku MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fotosenzibilizující látky MeSH
• metaloporfyriny * MeSH
• porfyriny * MeSH
• reaktivní formy kyslíku MeSH
• zinc-tetrakis(p-sulfonatophenyl)porphyrin MeSH Prohlížeč

As resistance of bacterial strains to antibiotics is a major problem, there is a need to look for alternative treatments. One option is antimicrobial photodynamic inactivation (aPDI). The pathogenic cells are targeted by a nontoxic photosensitizer while the surrounding healthy tissue is relatively unaffected. The photosensitizer is activated by light of t appropriate wavelength resulting in the generation of reactive oxygen species that are cytotoxic for the pathogens. In this work, the photosensitizer TMPyP and silver nanoparticles (AgNPs) were investigated for their synergistic antibacterial effect. We tested these two substances on two bacterial strains, methicillin-resistant Staphylococcus aureus 4591 (MRSA) and extended-spectrum beta-lactamases-producing Klebsiella pneumoniae 2486 (ESBL-KP), to compare their effectiveness. The bacteria were first incubated with TMPyP for 45 min or 5 h, then irradiated with a LED source with the total fluence of 10 or 20 J/cm2 and then placed in a microbiological growth medium supplemented with AgNPs. To accomplish the synergistic effect, the optimal combination of TMPyP and AgNPs was estimated as 1.56-25 μM for TMPyP and 3.38 mg/l for AgNPs in case of MRSA and 1.56-50 μM for TMPyP and 3.38 mg/l for AgNPs in case of ESBL-KP at 45 min incubation with TMPyP and fluence of 10 J/cm2. Longer incubation and/or longer irradiation led to a decrease in the maximum values of the photosensitizer concentration to produce the synergistic effect. From this work it can be concluded that the combination of antimicrobial photodynamic inactivation with a treatment including silver nanoparticles could be a promising approach to treat bacterial infection.

• Klíčová slova
• Antimicrobial photodynamic inactivation (aPDI), Extended-spectrum beta-lactamases-producing, Klebsiella pneumoniae (ESBL-KP), Methicillin-resistant Staphylococcus aureus (MRSA), Photosensitizer (PS), Silver nanoparticles (AgNPs), Synergistic effect,
• MeSH
• antibakteriální látky farmakologie   MeSH
• antiinfekční látky * farmakologie   MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky farmakologie   MeSH
• Klebsiella pneumoniae MeSH
• kovové nanočástice * MeSH
• methicilin rezistentní Staphylococcus aureus * MeSH
• porfyriny * farmakologie   MeSH
• rezistence na methicilin MeSH
• stříbro farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiinfekční látky * MeSH
• fotosenzibilizující látky MeSH
• porfyriny * MeSH
• stříbro MeSH

We report the first exocyclically metallated tetrapyridinoporphyrazine, [tetrakis-(trans-Pt(NH3)2Cl)-tetra(3,4-pyrido)porphyrazine-zinc(ii)](NO3)4 (4), synthesized in a multistep synthesis starting from 3,4-pyridinedicarbonitrile (1). The synthetic procedure involved a platination reaction of the intermediate tetra(3,4-pyrido)porphyrazine-zinc(ii) (2), whereby the zinc(ii) enhanced the solubility of the intermediate enabling the platination reaction. A similar approach to synthesize [tetrakis-(trans-Pt(NH3)2Cl)-tetra(3,4-pyrido)porphyrazine](NO3)4 (5) failed due to the unsuitable solubility properties of the intermediate tetra(3,4-pyrido)porphyrazine (3). The final product 4 and the intermediates were characterized, the photochemical and photophysical properties were determined and the photocytotoxicities were investigated. We demonstrate that the platinated tetra-pyridinoporphyrazine 4 is a potential photosensitizer for photodynamic therapy (PDT).

• MeSH
• fluorescenční spektrometrie MeSH
• fotochemoterapie MeSH
• fotosenzibilizující látky chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory farmakoterapie   patologie   MeSH
• porfyriny chemická syntéza   chemie   farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• stereoizomerie MeSH
• světlo MeSH
• viabilita buněk účinky léků   MeSH
• zinek chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fotosenzibilizující látky MeSH
• porfyriny MeSH
• reaktivní formy kyslíku MeSH
• zinek MeSH

The preparation of light-activated hybrid antibacterial agent combining the porphyrin molecules, bound to the silver nanoparticles (AgNPs) surface is reported. AgNPs were synthesized by N-methyl-2-pyrrolidone-initiated reduction without additional reducing agents. The chemical structure of protoporphyrin IX was modified with the aim to introduce thiol groups. The size distribution and shape features of AgNPs were checked using TEM and HRTEM microscopies. The introduction of thiol groups into the porphyrin was proved by IR spectroscopy. The AgNPs-porphyrin binding was performed in solution and confirmed by fluorescence quenching, Raman spectroscopy and energy-filtered transmission electron microscopy (EFTEM). The antibacterial tests were performed against S. epidermidis and E. coli upon to LED illumination and in the dark. The synergetic effect of AgNPs and porphyrin as well as light activation of the created antibacterial conjugates were observed.

• Klíčová slova
• Antibacterial, Light-triggered, Porphyrin, Silver nanoparticles,
• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• Escherichia coli účinky léků   MeSH
• kovové nanočástice chemie   ultrastruktura   MeSH
• luminiscence MeSH
• mikrobiální testy citlivosti MeSH
• porfyriny chemická syntéza   chemie   farmakologie   MeSH
• Staphylococcus epidermidis účinky léků   MeSH
• stříbro chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• porfyriny MeSH
• stříbro MeSH

The development of effective photosensitizers is particularly attractive for photodynamic therapy of cancer. Three novel porphyrin photosensitizers functionalized with phosphinic groups were synthesized and their physicochemical, photophysical, and photobiological properties were collected. Phosphinic acid groups (R1R2POOH) attached to the porphyrin moiety (R1) contain different R2 substituents (methyl, isopropyl, phenyl in this study). The presence of phosphinic groups does not influence absorption and photophysical properties of the porphyrin units, including the O2(1Δg) productivity. In vitro studies show that these porphyrins accumulate in cancer cells, are inherently nontoxic, however, exhibit high phototoxicity upon irradiation with visible light with their phototoxic efficacy tuned by R2 substituents on the phosphorus centre. Thus, phosphinatophenylporphyrin with isopropyl substituents has the strongest photodynamic efficacy due to the most efficient cellular uptake. We demonstrate that these porphyrins are attractive candidates for photodynamic applications since their photodynamic efficacy can be easily tuned by the R2 substituent.

• MeSH
• fotochemoterapie * MeSH
• fotosenzibilizující látky chemie   metabolismus   farmakologie   MeSH
• HeLa buňky MeSH
• lidé MeSH
• lidský sérový albumin metabolismus   MeSH
• porfyriny chemie   metabolismus   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fotosenzibilizující látky MeSH
• lidský sérový albumin MeSH
• porfyriny MeSH