[et_pb_section fb_built=”1″ _builder_version=”4.9.4″ _module_preset=”default” background_enable_image=”off” custom_padding=”2px||12px|||” global_module=”509″ saved_tabs=”all” global_colors_info=”{}”][et_pb_row use_custom_gutter=”on” gutter_width=”1″ _builder_version=”4.16″ _module_preset=”default” width=”100%” max_width=”100%” custom_padding=”4px|||||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_divider divider_weight=”60px” _builder_version=”4.16″ _module_preset=”default” width=”100%” max_width=”100%” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][lwp_divi_breadcrumbs home_text=”Inicio” use_before_icon=”off” link_color=”#89B7CA” current_text_color=”#001733″ _builder_version=”4.18.0″ _module_preset=”default” custom_padding=”||0px|||” global_colors_info=”{}”][\/lwp_divi_breadcrumbs][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” custom_padding=”0px||5px|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ _module_preset=”default” custom_padding=”||6px|||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.18.0″ _module_preset=”default” locked=”off” global_colors_info=”{}”]<\/p>\n
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P3: Nanotechnology for healthcare<\/p>\n
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Cancer is one of the leading causes of death worldwide. Despite large efforts invested into targeted- and immuno-therapies, reality shows that at least one potent cytotoxic is a must-have in the therapeutic regime.<\/p>\n
Transition metal chemistry offers extraordinary features to the rational design of candidate metallodrugs, such as a variety of available interactions (H-bond, pi-stacking, coordinative bond, supramolecular recognition), and unique redox behaviours, including catalysis.<\/p>\n
However, very few metallodrugs have been successfully translated into the clinic. There is a tremendous gap between knowing the structure of the metal-based drug candidate, its chemical behavior in aqueous solution and how it relates to cytotoxicity. For most metallodrugs, we do not even know where they are located inside the cell, and which targets they have. This gap is undoubtedly the major challenge in their pre-clinical development.<\/p>\n
This PhD project will focus on imaging selected potent metallodrugs in the nanospace of the human cell at state-of-the-art intracellular resolution in cryogenic conditions. We are developing some of the most potent metallodrugs that there are (Figure 1), and have label them with fluorophores for optical microscopy. Moreover, we are also implementing correlative approaches combining different imaging techniques including fluorescence, X-ray and electron imaging. Using this new pipelines we will depict the intracellular journey \u2013in a time line\u2013 of selected metallodrugs and reveal where they exert their deadly effect. Additional single-cell experiments will require regular visits at synchrotron radiation facilities (cryo-SXT and -XRF, at ALBA, Spain, and ESRF, France, respectively). Complementary placements at industrial collaborators interested in developing imaging techniques are anticipated.<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_3,1_3,1_3″ _builder_version=”4.18.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”1_3″ _builder_version=”4.18.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_image src=”https:\/\/idealcofund-project.eu\/phd\/wp-content\/uploads\/2023\/01\/Unveiling-the-Intracellular-Journey-of-Potent-Metallodrugs.png” title_text=”Unveiling the Intracellular Journey of Potent Metallodrugs” align=”right” _builder_version=”4.18.0″ _module_preset=”default” width=”82.4%” global_colors_info=”{}”][\/et_pb_image][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.18.0″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.18.0″ _module_preset=”default” custom_padding=”289px||||false|false” global_colors_info=”{}”]<\/p>\n
Figure 1. Intracellular allocation of an Ir metallodrug in MCF7 cells by means of cryo-SXT and cryo-XRF.<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_3″ _builder_version=”4.18.0″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” custom_padding=”||91px|||” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text disabled_on=”off|off|off” _builder_version=”4.18.0″ _module_preset=”default” custom_margin=”||29px|||” custom_padding=”0px|||||” global_colors_info=”{}”]<\/p>\n The candidate will have strong synthetic skills, in particular in the synthesis of fluorophores. Although experience with cell cultures is not required an understanding of the human cell and a good grasp of molecular biology will be valued. Expertise in optical, X-ray nor electron microscopy is not a requirement but a strong interest in imaging techniques and in 3D correlative data analysis is necessary to success in this PhD project.<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.18.0″ _module_preset=”default” custom_margin=”||29px||false|false” custom_padding=”0px||||false|false” global_colors_info=”{}”]<\/p>\n We take advantage of metal coordination and organometallic chemistry principles to design novel potent metallodrugs. We aim to modulate \u2013at the molecular level\u2013 the cancer cell machinery in a controlled manner.\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0<\/p>\n In a framework of medicinal chemistry, we explore the transition metal block of the periodic table to produce new metallo-organic drug candidates to ultimately halt cancer progression and stop invasion. We focus on cytotoxic activity in conjunction to switchability (activation and deactivation of the pharmacophore). Among our best candidates are Ir, Os, Ru, and Rh complexes.<\/p>\n For our rational design approach, we develop techniques that help us track the intracellular journey of our metallodrugs within the cell and in a timeline. We seek to combine bulk cell experiments with developmental methodologies based on cryo-single cell techniques.<\/p>\n Our most explorative approach focuses on the use of nanomaterials to enhance specific properties of our drug candidates, such as in-cell catalysis.<\/p>\n [\/et_pb_text][et_pb_text _builder_version=”4.18.0″ _module_preset=”default” custom_margin=”||29px||false|false” custom_padding=”0px||||false|false” global_colors_info=”{}”]<\/p>\n Prof. Ana Mar\u00eda Pizarro Research Group website:https:\/\/nanociencia.imdea.org\/metallodrugs-to-modulate-cancer-cell-machinery\/group-home<\/a>\u00a0<\/p>\n [\/et_pb_text][et_pb_code _builder_version=”4.18.0″ _module_preset=”default” locked=”off” global_colors_info=”{}”]Tweet<\/a>APPLICANT’S REQUIREMENTS<\/strong><\/h2>\n
RESEARCH GROUP DESCRIPTION<\/strong><\/h2>\n
RESEARCH SUPERVISOR<\/strong><\/h2>\n
ana.pizarro@imdea.org<\/a>\u00a0<\/p>\n