Lecture
Novel bioanalytical tools to address individual cell behavior in pharmacological studies
- 11.04.2024 at 09:30 - 10:00
- ICM Saal 5
- Language: English
- Type: Lecture
Lecture description
The positive chemotherapeutic effect of cisplatin in most cancers (e.g., ovarian, prostate, etc.) is hampered by inherent and acquired drug resistance, a multifactorial and still not well characterized process. In fact, several mechanisms have been suggested to participate in conferring platinum-resistant properties to a tumor cell, such as genetic alterations in genes involved in drug uptake (and efflux), DNA repair, autophagy, apoptosis, and cell cycle control pathways [1]. In order to overcome some of these drawbacks, particularly those related to the reduced drug uptake, different combinations of cisplatin (or cisplatin precursors/prodrugs) to nanostructures that permit efficient drug uptake are being widely investigated. Among them, nanodelivery systems including metallic nanoparticles show the capability to incorporate cisplatin (IV) prodrugs. Ultrasmall iron oxide nanoparticles (<10 NM)="" HAVE="" BEEN="" LOADED="" WITH="" CIS-DIAMMINETETRACHLOROPLATINUM="" (IV),="" A="" CISPLATIN="" (II)="" PRODRUG,="" AND="" USED="" AS="" EFFICIENT="" NANODELIVERY="" SYSTEM="" IN="" CELL="" MODELS.="" INITIAL="" RESULTS="" REGARDING="" THE="" CELLULAR="" INCORPORATION="" OF="" THIS="" NANOTRANSPORTER,="" BY="" USING="" INDUCTIVELY="" COUPLED="" PLASMA="" MASS="" SPECTROMETRIC="" (ICP-MS)="" APPROACHES="" WITH="" SINGLE="" CELL="" SAMPLE="" INTRODUCTION="" SYSTEMS="" REVEALED="" A="" SIGNIFICANTLY="" HIGHER="" UPTAKE="" WITH="" RESPECT="" TO="" CISPLATIN="" IN="" OVARIAN="" CELLS="">
In this presentation, we will show the extension of the work to different cell models of ovarian cancer and osteosarcoma. To address the effect of the Pt incorporation in the apoptotic cellular status, fluorescent activated cell sorting experiments will be off-line connected to SC-ICP-MS experiments. Therefore, the differences on the Pt-content of the viable/apoptotic/necrotic cells will be also illustrated in order to address possible differences in the mechanisms of actions of the different metallodrugs assayed. In addition, the proposed nanodelivery system will be tested in novel 3-dimensional cell culture systems which more closely resemble the in vivo biology. Spheroids obtained from scaffold-free techniques including hanging drop microplates using osteosarcoma cell lines will be tested to address the platination level of the cells using the proposed nanocarrier in comparison to cisplatin. This type of experiments, will provide information on the penetration rate of the nanocarrier and should resemble, more closely, the in vivo behavior of the nanotransporter.
[1] Galluzzi, L.; Vitale, I.; Michels, J.; Brenner, C.; Szabadkai, G.; Harel-Bellan, A.; Castedo, M.; Kroemer, G. Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 2014, 5, e1257.
In this presentation, we will show the extension of the work to different cell models of ovarian cancer and osteosarcoma. To address the effect of the Pt incorporation in the apoptotic cellular status, fluorescent activated cell sorting experiments will be off-line connected to SC-ICP-MS experiments. Therefore, the differences on the Pt-content of the viable/apoptotic/necrotic cells will be also illustrated in order to address possible differences in the mechanisms of actions of the different metallodrugs assayed. In addition, the proposed nanodelivery system will be tested in novel 3-dimensional cell culture systems which more closely resemble the in vivo biology. Spheroids obtained from scaffold-free techniques including hanging drop microplates using osteosarcoma cell lines will be tested to address the platination level of the cells using the proposed nanocarrier in comparison to cisplatin. This type of experiments, will provide information on the penetration rate of the nanocarrier and should resemble, more closely, the in vivo behavior of the nanotransporter.
[1] Galluzzi, L.; Vitale, I.; Michels, J.; Brenner, C.; Szabadkai, G.; Harel-Bellan, A.; Castedo, M.; Kroemer, G. Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 2014, 5, e1257.
All lectures within this session
- 09:30 - 10:00Novel bioanalytical tools to address individual cell behavior in pharmacological studies
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