Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00503707" target="_blank" >RIV/61388963:_____/19:00503707 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388980:_____/19:00503707

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlelanding/2019/BM/C8BM01564C#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2019/BM/C8BM01564C#!divAbstract</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c8bm01564c" target="_blank" >10.1039/c8bm01564c</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities

Popis výsledku v původním jazyce

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 clusterncomplexes, 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 photodynamicntherapy 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 rapidlyninternalized 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.

Název v anglickém jazyce

Cationic octahedral molybdenum cluster complexes functionalized with mitochondria-targeting ligands: photodynamic anticancer and antibacterial activities

Popis výsledku anglicky

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 clusterncomplexes, 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 photodynamicntherapy 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 rapidlyninternalized 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

<a href="/cs/project/GA18-05076S" target="_blank" >GA18-05076S: Biomateriály obsahující oktaedrické molybdenové klastry jako radiosensitizátory singletového kyslíku</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biomaterials Science

ISSN

2047-4830

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

1386-1392

Kód UT WoS článku

000463746600011

EID výsledku v databázi Scopus

2-s2.0-85063465108