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Microtubule network as a potential candidate for targeting by gold nanoparticle-assisted photothermal therapy
摘要： Photothermal therapy is achieving ever-increasing attention as a promising method for killing cancer cells. Although, gold nanoparticles are regarded as one of the most effective photothermal therapy agents, the mechanisms underlying their action have to be addressed. Moreover, studies have showed that gold nanoparticles induce apoptosis in treated cultures. Hence, in this study, we investigated the interaction of folic acid functionalized gold nanoparticles and gold-shelled Fe3O4 nanoparticles with microtubule and microtubule associated protein tau in order to introduce intracellular targets of these nanoparticles and provide a holistic view about the mechanism of action of gold nanoparticles used in photothermal therapy. Various spectroscopic methods were used to find gold nanoparticles interaction with Tubulin and Tau. Our results indicated that these gold nanoparticles interact with both Tau and Tubulin and their affinity increases as temperature rises. Also, the results illustrated that quenching mechanism for gold nanoparticles interaction with Tubulin and Tau was static. The hydrophobic interaction was determined as driving force for gold nanoparticles binding to Tubulin and Tau. Moreover, it was showed that both type of gold nanoparticles stabilize microtubule polymers. These results suggest Tau and Tubulin as intracellular target of gold nanoparticles and propose that microtubule network is at the heart of apoptosis mechanisms initiated by photothermal therapy.
关键词： Gold-shelled Fe3O4 nanoparticles,Tubulin,Gold nanoparticles,Tau protein,Photothermal therapy
更新于2025-09-19 17:15:36
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In vivo comparison of N-11CH3 vs O-11CH3 radiolabeled microtubule targeted PET ligands
摘要： Altered dynamics of microtubules (MT) are implicated in the pathophysiology of a number of brain diseases. Therefore, radiolabeled MT targeted ligands that can penetrate the blood brain barrier (BBB) may offer a direct and sensitive approach for diagnosis, and assessing the clinical potential of MT targeted therapeutics using PET imaging. We recently reported two BBB penetrating radioligands, [11C]MPC-6827 and [11C]HD-800 as specific PET ligands for imaging MTs in brain. The major metabolic pathway of the above molecules is anticipated to be via the initial labeling site, O-methyl, compared to the N-methyl group. Herein, we report the radiosynthesis of N-11CH3-MPC-6827 and N-11CH3-HD-800 and a comparison of their in vivo binding with the corresponding O-11CH3 analogues using microPET imaging and biodistribution methods. Both O-11CH3 and N-11CH3 labeled MT tracers exhibit high specific binding and brain. The N-11CH3 labeled PET ligands demonstrated similar in vivo binding characteristics compared with the corresponding O-11CH3 labeled tracers, [11C]MPC-6827 and [11C]HD-800 respectively.
关键词： brain,PET,microtubule,tubulin,radiotracer
更新于2025-09-16 10:30:52
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Localization microscopy at doubled precision with patterned illumination
摘要： MINFLUX offers a breakthrough in single molecule localization precision, but is limited in field of view. Here we combine centroid estimation and illumination pattern induced photon count variations in a conventional widefield imaging setup to extract position information over a typical micrometer-sized field of view. We show a near two-fold improvement in precision over standard localization with the same photon count on DNA-origami nanostructures and tubulin in cells, using DNA-PAINT and STORM imaging.
关键词： DNA-origami,DNA-PAINT,patterned illumination,tubulin,STORM,Localization microscopy
更新于2025-09-12 10:27:22
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Discrimination of <i>Aspergillus flavus</i> from <i>Aspergillus oryzae</i> by matrix‐assisted laser desorption/ionisation time‐of‐flight (MALDI‐TOF) mass spectrometry
摘要： Background: Aspergillus flavus is a major cause of severe non‐invasive fungal infections in the Middle Eastern countries. However, it is difficult to distinguish A flavus from A oryzae. Objectives: To assess the potential of matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry (MALDI‐TOF MS) in discriminating between A flavus and A oryzae and compare it with β‐tubulin gene sequencing. Methods: We used the Bruker Daltonik MALDI‐TOF MS system to analyse 200 clinical and environmental A flavus isolates and one A pseudonomius and one A alliaceus (Aspergillus section Flavi) isolate a priori identified as such by sequencing of the β‐tubulin gene. Results: All 200 A flavus isolates were identified at the genus level and 176 (88%) at the species levels by MALDI‐TOF MS based on the spectral log‐scores (≥2.0 and 1.7‐1.99, respectively); among them, only 18 (10.2%) were confirmed as A flavus, whereas 35 (19.9%) were identified as A oryzae and 123 (69.9%) as A flavus/A oryzae. Aspergillus pseudonomius and A alliaceus were misidentified as A flavus and A parasiticus with log‐score values of 1.39 and 1.09, respectively. Conclusions: The results indicate that the commercially available Bruker Daltonik MALDI‐TOF MS score database cannot separate A flavus and A oryzae species. We also showed that establishment of an in‐house library is a useful tool to discriminate closely related Aspergillus species, including A flavus and A oryzae.
关键词： identification,MALDI‐TOF MS,β‐tubulin,Aspergillus oryzae,Aspergillus flavus
更新于2025-09-11 14:15:04