Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články
PubMed
30656318
DOI
10.1039/c8bm01564c
Knihovny.cz E-zdroje
- MeSH
- antibakteriální 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
- 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
- protinádorové látky chemická syntéza chemie farmakologie MeSH
- screeningové testy protinádorových léčiv 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
- Názvy látek
- antibakteriální látky MeSH
- kationty MeSH
- ligandy MeSH
- molybden MeSH
- organokovové sloučeniny MeSH
- protinádorové látky MeSH
- singletový kyslík 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.
Citace poskytuje Crossref.org
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