The emergence of multidrug-resistant microbial pathogens poses a significant threat, severely limiting the options for effective antibiotic therapy. This challenge can be overcome through the photoinactivation of pathogenic bacteria using materials generating reactive oxygen species upon exposure to visible light. These species target vital components of living cells, significantly reducing the likelihood of resistance development by the targeted pathogens. In our research, we have developed a nanocomposite material consisting of an aqueous colloidal suspension of graphene oxide sheets adorned with nanoaggregates of octahedral molybdenum cluster complexes. The negative charge of the graphene oxide and the positive charge of the nanoaggregates promoted their electrostatic interaction in aqueous medium and close cohesion between the colloids. Upon illumination with blue light, the colloidal system exerted a potent antibacterial effect against planktonic cultures of Staphylococcus aureus largely surpassing the individual contributions of the components. The underlying mechanism behind this phenomenon lies in the photoinduced electron transfer from the nanoaggregates of the cluster complexes to the graphene oxide sheets, which triggers the generation of reactive oxygen species. Thus, leveraging the unique properties of graphene oxide and light-harvesting octahedral molybdenum cluster complexes can open more effective and resilient antibacterial strategies.
- MeSH
- antibakteriální látky farmakologie MeSH
- lidé MeSH
- molybden farmakologie MeSH
- reaktivní formy kyslíku MeSH
- stafylokokové infekce * MeSH
- Staphylococcus aureus * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The development of singlet oxygen photosensitizers, which target specific cellular organelles, constitutes a pertinent endeavor to optimize the efficiency of photodynamic therapy. Targeting of the cell membrane eliminates the need for endocytosis of drugs that can lead to toxicity, intracellular degradation, or drug resistance. In this context, we utilized copper-free click chemistry to prepare a singlet oxygen photosensitizing complex, made of a molybdenum-iodine nanocluster stabilized by triazolate apical ligands. In phosphate-buffered saline, the complex formed nanoaggregates with a positive surface charge due to the protonatable amine function of the apical ligands. These nanoaggregates targeted cell membranes and caused an eminent blue-light phototoxic effect against HeLa cells at nanomolar concentrations, inducing apoptotic cell death, while having no dark toxicity at physiologically relevant concentrations. The properties of this complex were compared to those of a negatively charged parent complex to highlight the dominant effect of the nature of apical ligands on biological properties of the nanocluster. These two complexes also exerted (photo)antibacterial effects on several pathogenic strains in the form of planktonic cultures and biofilms. Overall, we demonstrated that the rational design of apical ligands toward cell membrane targeting leads to enhanced photodynamic efficiency.
- MeSH
- buněčná membrána MeSH
- HeLa buňky MeSH
- jod * farmakologie MeSH
- lidé MeSH
- ligandy MeSH
- molybden * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Octahedral molybdenum cluster complexes have recently come forth as pertinent singlet oxygen photosensitizers towards biological applications. Still, their phototoxic efficiency in the absence of nanocarriers remains limited due to their poor cellular uptake. Here, two cationic octahedral molybdenum cluster complexes, bearing carboxylate ligands with triphenylphosphonium (1) or N-methyl pyridinium (2) mitochondria-targeting terminal functions, have been designed and synthesized. Their photophysical properties in water and in vitro biological activity were investigated in the context of blue-light photodynamic therapy of cancer and photoinactivation of bacteria. Upon blue light irradiation, complex 1 displays red luminescence with a quantum yield of 0.24 in water, whereas complex 2 is much less emissive (ΦL < 0.01). Nevertheless, both complexes efficiently produce singlet oxygen, O2(1Δg). Complex 1 is rapidly internalized into HeLa cells and accumulated in mitochondria, followed by relocation to lysosomes and clearance at longer times. In contrast, the more hydrophilic 2 is not internalized into HeLa cells, highlighting the effect of the apical ligands on the uptake properties. The treatment with 1 results in an intensive phototoxic effect under 460 nm irradiation (IC50 = 0.10 ± 0.02 μM), which exceeds by far those previously reported for octahedral cluster-based molecular photosensitizers. The ratio between phototoxicity and dark toxicity is approximately 50 and evidences a therapeutic window for the application of 1 in blue-light photodynamic therapy. Complex 1 also enters and efficiently photoinactivates Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus, documenting its suitability as a blue-light photosensitizer for antimicrobial applications.
- MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- fotochemoterapie * MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- HeLa buňky MeSH
- kationty chemická syntéza chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- ligandy MeSH
- mikrobiální testy citlivosti MeSH
- mitochondrie účinky léků MeSH
- molekulární struktura MeSH
- molybden chemie farmakologie MeSH
- organokovové sloučeniny chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- singletový kyslík chemie metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The spatiotemporal sensing of specific cationic and anionic species is crucial for understanding the processes occurring in living systems. Herein, we developed new fluorescence sensors derived from tetrapyrazinoporphyrazines (TPyzPzs) with a recognition moiety that consists of an aza-crown and supporting substituents. Their sensitivity and selectivity were compared by fluorescence titration experiments with the properties of known TPyzPzs (with either one aza-crown moiety or two of these moieties in a tweezer arrangement). Method of standard addition was employed for analyte quantification in saliva. For K+ recognition, the new derivatives had comparable or larger association constants with larger fluorescence enhancement factors compared to that with one aza-crown. Their fluorescence quantum yields in the ON state were 18× higher than that of TPyzPzs with a tweezer arrangement. Importantly, the sensitivity toward cations was strongly dependent on counteranions and increased as follows: NO3- < Br- < CF3SO3- < ClO4- ≪ SCN-. This trend resembles the chaotropic ability expressed by the Hofmeister series. The high selectivity toward KSCN was explained by synergic association of both K+ and SCN- with TPyzPz sensors. The sensing of SCN- was further exploited in a proof of concept study to quantify SCN- levels in the saliva of a smoker and to demonstrate the sensing ability of TPyzPzs under in vitro conditions.
- MeSH
- crown ethery chemická syntéza chemie MeSH
- draslík analýza MeSH
- fluorescence MeSH
- fluorescenční barviva chemická syntéza chemie MeSH
- fluorescenční mikroskopie metody MeSH
- fluorescenční spektrometrie metody MeSH
- HeLa buňky MeSH
- kuřáci MeSH
- lidé MeSH
- limita detekce MeSH
- metaloporfyriny chemická syntéza chemie MeSH
- sliny chemie MeSH
- thiokyanatany analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
This review aims to summarize the current status of photoactivatable nanostructured film and polymeric nanofiber surfaces used in biomedical applications with emphasis on their photoantimicrobial activity, oxygen-sensing in biological media, light-triggered release of drugs, and physical or structural transformations. Many light-responsive functions have been considered as novel ways to alter surfaces, i.e., in terms of their reactivities and structures. We describe the design of surfaces, nano/micro-fabrication, the properties affected by light, and the application principles. Additionally, we compare the various approaches reported in the literature.
- MeSH
- fotochemie * MeSH
- nanostruktury * MeSH
- povrchové vlastnosti MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The formation of self-assemblies between CdSe quantum dots (QDs) and Zn phthalocyanines (Pc) and azaphthalocyanines (AzaPc) bearing alkylsulfanyl substituents and the photophysical properties of these assemblies were studied using both steady-state and time-resolved luminescence/absorption spectroscopy. The formation of the self-assemblies was accompanied by a blue shift of the Q band of the dyes and by a quenching of the CdSe QDs luminescence. The largest spectral shift of the Q-band was approximately 7 nm and was observed for pentan-3-ylsulfanyl-functionalised phthalocyanine (). Assuming a 1 : 1 stoichiometry, the calculated binding constant was 4 × 10(4) M(-1). Pc substituted with the bulky tert-butylsulfanyl groups (1) exhibited a smaller shift of the Q band. The quenching of the CdSe QDs luminescence by 1 was more effective than that observed for 3. The results indicated that the luminescence quenching may be due to a photoinduced charge transfer between 1 or 3 and the CdSe QDs. In contrast, the AzaPc (2) with the same substituents as 1 had little effect on the QDs luminescence. For all cases, we found an inefficient resonance energy transfer between the attached dyes and the CdSe QD. The formation of the self-assemblies had negligible effects on the photogeneration of the singlet oxygen, O2((1)Δg), that was fully controlled only by the absorption of the light by the macrocycles.
- MeSH
- fluorescenční spektrometrie MeSH
- indoly chemie MeSH
- kvantová teorie MeSH
- kvantové tečky * MeSH
- organokovové sloučeniny chemie MeSH
- rozpouštědla chemie MeSH
- sloučeniny kadmia chemie MeSH
- sloučeniny selenu chemie MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Novel biomaterials based on hydrophilic polycaprolactone and polyurethane (Tecophilic®) nanofibers with an encapsulated 5,10,5,20-tetraphenylporphyrin photosensitizer were prepared by electrospinning. The doped nanofiber textiles efficiently photo-generate O(2)((1)Δ(g)), which oxidize external chemical and biological substrates/targets. Strong photo-virucidal effects toward non-enveloped polyomaviruses and enveloped baculoviruses were observed on the surface of these textiles. The photo-virucidal effect was confirmed by a decrease in virus infectivity. In contrast, no virucidal effect was detected in the absence of light and/or the encapsulated photosensitizer.
- MeSH
- anthraceny chemie MeSH
- antivirové látky farmakologie MeSH
- Baculoviridae účinky léků MeSH
- fotosenzibilizující látky farmakologie MeSH
- inaktivace viru účinky léků MeSH
- kapsida chemie MeSH
- myši MeSH
- nanovlákna chemie ultrastruktura MeSH
- oxidace-redukce MeSH
- polyestery chemie MeSH
- Polyomavirus účinky léků MeSH
- polyurethany chemie MeSH
- porfyriny farmakologie MeSH
- rekombinace genetická genetika MeSH
- singletový kyslík metabolismus MeSH
- textilie * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Electrospun polymeric nanofiber materials doped with 5,10,15,20-tetraphenylporphyrin (TPP) photosensitizer were prepared from four different polymers and were characterized with microscopic methods, steady-state, and time-resolved fluorescence and absorption spectroscopy. The polymers used included polyurethane Larithane™ (PUR), polystyrene (PS), polycaprolactone (PCL), and polyamide 6 (PA6). The antibacterial activity of all nanofiber materials against E. coli was activated by visible light and it was dependent on oxygen permeability/diffusion coefficients and the diameter of the polymeric nanofibers. This activity is based on oxidation ability of singlet oxygen O₂(¹Δ(g)) that is generated upon irradiation. All tested nanofiber materials exhibited prolonged antibacterial properties, even in the dark after long-duration irradiation. The post-irradiation effect was explained by the photogeneration of H₂O₂, which provided the material with long-lasting antibacterial properties.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Escherichia coli účinky léků MeSH
- fotosenzibilizující látky chemie MeSH
- kaprolaktam analogy a deriváty chemie MeSH
- nanovlákna chemie MeSH
- oxidancia chemie MeSH
- peroxid vodíku chemie MeSH
- polyestery chemie MeSH
- polymery chemie MeSH
- polystyreny chemie MeSH
- polyurethany chemie MeSH
- porfyriny chemie MeSH
- singletový kyslík chemie MeSH
- světlo MeSH
- testování materiálů MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
