Development of novel GnRH and Tat48–60 based luminescent probes with enhanced cellular uptake and bioimaging profile
| العنوان: | Development of novel GnRH and Tat48–60 based luminescent probes with enhanced cellular uptake and bioimaging profile |
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| المؤلفون: | Rajshekhar Karpoormath, Michalis D. Mantzaris, Ab Majeed Ganai, Carol Murphy, Mariana Sakka, Anastasia Kougioumtzi, Georgios Vartholomatos, Nisar Sayyad, Eirinaios I. Vrettos, Panagiotis Stathopoulos, Vassilios Tsikaris, Maria V. Chatziathanasiadou, Theodore Lazarides, Andreas G. Tzakos |
| المصدر: | Dalton Transactions. 50:9215-9224 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | chemistry.chemical_classification, 0303 health sciences, biology, chemistry.chemical_element, Peptide, 010402 general chemistry, biology.organism_classification, 01 natural sciences, Fluorescence, 0104 chemical sciences, law.invention, Ruthenium, Inorganic Chemistry, HeLa, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Confocal microscopy, law, Biophysics, Peptide bond, Fluorescein, 030304 developmental biology, Conjugate |
| الوصف: | There is a clear need to develop photostable chromophores for bioimaging with respect to the classically utilized green fluorescent dye fluorescein. Along these lines, we utilized a phosphorescent carboxy-substituted ruthenium(ii) polypyridyl [Ru(bipy)2(mcb)]2+ (bipy = 2,2'-bipyridyl and mcb = 4-carboxy-4'-methyl-2,2'-bipyridyl) complex. We developed two luminescent peptide conjugates of the cell-penetrating peptide Tat48-60 consisting of either [Ru(bipy)2(mcb)]2+ or 5(6)-carboxyfluorescein (5(6)-FAM) tethered on the Lys50 of the peptide through amide bond. We confirmed the efficient cellular uptake of both bioconjugates in HeLa cells by confocal microscopy and flow cytometry and proved that the ruthenium-based chromophore possesses enhanced photostability compared to a 5(6)-FAM-based peptide, after continuous laser scanning. Furthermore, we designed and developed a luminescent agent with high photostability, based on the ruthenium core, that could be selectively localized in cancer cells overexpressing the GnRH receptor (GnRH-R). To achieve this, we took advantage of the tumor-homing character of d-Lys6-GnRH which selectively recognizes the GnRH-R. The [Ru(bipy)2(mcb)]2+-d-Lys6-GnRH peptide conjugate was synthesized, and its cellular uptake was evaluated through flow cytometric analysis and live-cell imaging in HeLa and T24 bladder cancer cells as negative and positive controls of GnRH-R, respectively. Besides the selective targeting that the specific conjugate could offer, we also recorded high internalization levels in T24 bladder cancer cells. The ruthenium(ii) polypyridyl peptide-based conjugates we developed is an intriguing approach that offers targeted cell imaging in the Near Infrared region, and simultaneously paves the way for further advancements in the dynamic studies on cellular imaging. |
| تدمد: | 1477-9234 1477-9226 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::e3160ac31b6d28f415b75191af853cec https://doi.org/10.1039/d1dt00060h |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........e3160ac31b6d28f415b75191af853cec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779234 14779226 |
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