ABSTRACT
Supramolecular hybrids of graphene quantum dots (GQDs) and phthalocyanine (Pc) dyes were studied as turn-OFF-ON photoluminescence nanosensors for detection of ds-DNA. Pcs with four (Pc4) and eight (Pc8) positive charges were selected to interact with negatively charged GQDs. The photoluminescence of the GQDs was quenched upon interaction with the Pcs, due to the formation of non-emissive complexes. In the presence of ds-DNA, the Pcs interacted preferentially with the negatively charged ds-DNA, lifting the quenching effect over the photoluminescence of the GQDs and restoring their emission intensity. The best performance as a sensor of ds-DNA was registered for the GQD-Pc8, with a limit of detection (LOD) in the picomolar range. The LOD for GQD-Pc8 was more than one order of magnitude lower and its sensitivity was about a factor of three higher than that of the analogue GQD-Pc4 nanosensor. The sensitivity and selectivity of this simple GQD-Pc8 nanosensor is comparable to those of the more sophisticated carbon-based nanosensors for DNA reported previously.
ABSTRACT
Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600-700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.
ABSTRACT
OBJECTIVES: Sulpiride and melatonin decrease dopamine activity. Sulpiride, a D2 antagonist of dopamine receptors, and melatonin, a pineal substance with antidopaminergic action, are administered to tinnitus patients to decrease tinnitus perception. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study was done. SETTING: General otorhinolaryngologic consultation for 2002-2004 in Seville, Spain. METHODS: One hundred twenty patients consulted for subjective tinnitus. They were included randomly in four groups of 30. One group took sulpiride (50 mg/8 h) alone, the second group took melatonin (3 mg/24 h), the third group took the same doses of sulpiride (50 mg/8 h) plus melatonin (3 mg/24 h), and the fourth group took placebo (lactose 50 mg/8 h), all for 1 month. Ninety-nine patients completed the study. MAIN OUTCOME MEASURES: Clinical history, tonal audiometry, tympanometry, and tinnitometry were done at the beginning and end of the study. Subjective grading of tinnitus perception and a visual analogue scale (0-10) were done for evaluation of results. RESULTS: Based on the subjective grading, tinnitus perception diminished by 56% in patients treated with sulpiride, by 40% in patients treated with melatonin, by 81% in patients treated with sulpiride plus melatonin, and by 22% in patients treated with placebo. Based on the visual analogue scale, tinnitus perception diminished from 7.7 to 6.3 in patients treated with sulpiride, to 6.5 in those treated with melatonin, to 4.8 in patients treated with sulpiride plus melatonin, and to 7.0 in those treated with placebo. CONCLUSIONS: Sulpiride and melatonin reduce tinnitus perception, decreasing dopamine activity. The tinnitus auditolimbic dopaminergic pathway has broad therapeutic implications.
