RESUMO
Octahedral molybdenum and tungsten clusters have potential biological applications in photodynamic therapy and bioimaging. However, poor solubility and hydrolysis stability of these compounds hinder their application. The first water-soluble photoluminescent octahedral tungsten cluster [{W6 I8 }(DMSO)6 ](NO3 )4 was synthesised and demonstrated to be at least one order of magnitude more stable towards hydrolysis than its molybdenum analogue. Biological studies of the compound on larynx carcinoma cells suggest that it has a significant photoinduced toxicity, while the dark toxicity increases with the increase of the degree of hydrolysis. The increase of the dark toxicity is associated with the in situ generation of nanoparticles that clog up the cisternae of rough endoplasmic reticulum.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Molibdênio/química , Molibdênio/farmacologia , Tungstênio/química , Tungstênio/farmacologia , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Células Hep G2 , Humanos , Hidrólise , Luz , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologiaRESUMO
A selective fluorescent probe for Zn(ii), AQA-F, has been synthesized. AQA-F exhibits a ratiometric shift in emission of up to 80 nm upon binding Zn(ii) ([AQA-F] = 0.1 mM, [Zn(ii)Cl2] = 0-300 µM). An enhancement of quantum yield from Φ = 4.2% to Φ = 35% is also observed. AQA-F has a binding constant, Kd = 15.2 µM with Zn(ii). This probe has been shown to respond to endogenous Zn(ii) levels in vitro in prostate and prostate cancer cell lines. [18F]AQA-F has been synthesized with a radiochemical yield of 8.6% and a radiochemical purity of 97% in 88 minutes. AQA-F shows the potential for a dual modal PET/fluorescence imaging probe for Zn(ii).
Assuntos
Complexos de Coordenação/química , Corantes Fluorescentes/química , Microscopia de Fluorescência , Tomografia por Emissão de Pósitrons , Zinco/análise , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Radioisótopos de Flúor/química , Humanos , Marcação por Isótopo , Masculino , Próstata/patologia , Neoplasias da Próstata/patologia , Espectrometria de FluorescênciaRESUMO
A novel SERS/fluorescent multimodal imaging probe for mitochondria has been synthesised using 12â nm diameter gold nanoparticles (AuNP) surface functionalised with a rhodamine thiol derivative ligand. The normal pH-dependent fluorescence of the rhodamine-based ligand is inversed when it is conjugated with the AuNP and higher emission intensity is observed at basic pH. This switch correlates to a pKa at pHâ 6.62, which makes it an ideal candidate for a pH-sensitive imaging probe in the biological range (pHâ 6.5-7.4). The observed pH sensitivity of the ligand when attached to the AuNP is thought to be due to the formation of a spirolactam ring, going from positively charged (+18â mV) to negatively charged (-60â mV) as the pH is changed from acidic to basic. Additionally, conjugation of the ligand to the AuNP serves to enhance the Raman signal of the rhodamine ligand through surface-enhanced Raman scattering (SERS). Confocal microscopy has shown that the probe enters HEK293 (kidney), A2780 (ovarian cancer) and Min6 (pancreatic beta) cells within an hour and a half incubation time. The probe was shown to localise in the mitochondria, thus providing a novel pH-dependent SERS/fluorescent multimodal imaging probe for mitochondria.