PhD Student: \;Roger Gómez Herrera
\nIn pers on Event - Register HERE&n bsp\;to attend
\nDirecto rs: \;CSIC Research Prof. Daniel Ruiz Molina\, Nanostructured Functional Materia ls \;Group Leader and Dr Fernando Novio\, Associate Professor UAB.
\nShort Abstract:
Glioblastoma multiforme (GBM) is th e most aggressive primary brain tumour in adults. The current clinical sta ndard treatment\, established back in 2005\, includes surgical resection f ollowed by radiotherapy and temozolomide chemotherapy. Still\, GBM present s a median survival rate of less than two years and less than 6% five-year survival. This situation underscores the need to develop better therapeut ic agents. Pt compounds\, like cisplatin\, remain among the most potent an ticancer agents. However\, these drugs encounter obstacles in GBM due to b lood–brain barrier permeability\, systemic toxicities\, and resistance.< /p>\n
This Thesis develops on Pt-based drugs that address these barriers by exploring multi-target nanotherapies that improve tumour selectivity a nd targeting\, minimize systemic exposure\, while exploiting local therape utic windows. In these lines we investigate combination therapies\, and bi oinspired biomaterials as strategies to overcome these limitations. More s pecifically\, this Thesis focuses on four research lines whose novelty var ies as described next:
\nFirst\, Pt(IV) catechol-ba sed coordination nanoparticles (CNP) formed by oxidative polymerization of a Pt(IV) prodrug monomer (PtBC). This platform yields me lanin-like nanoparticles (NPs)\, a Trojan-horse approach for brain disease s\, with pH and redox-sensitive Pt(IV) release.
\nSecond\, squaraine (SQ)-based Pt(II) supramolecular NPs combining photoacti vated chemotherapy (PACT) and photodynamic (PDT) prospects of SQs. Accordi ng with the experimental results\, PACT was discarded while interesting PD T effects were found on SQ supramolecular NPs without Pt.
\nThird\, a bi-functional core-shell NP was designed with a superpa ramagnetic iron-oxide (SPION) core and a zirconium-based CNP shell bearing 9\,10-diphenylanthracene moieties. The shell is capable to store singlet oxygen under ultraviolet irradiation and release it on demand via magnetic hyperthermia (MHT) generated by the SPION core. In vitro studies on GL261 murine GBM model display a cooperative heat and reactive oxygen species (ROS) cytotoxicity effect. In vivo \;experiments demo nstrated the core-shell NP to be highly specific and sensitive to traverse relaxation weighted (T2w) magnetic resonance imaging. Unexpected ly\, the platform demonstrated as selective contrast agent for bladder at very low concentrations\, far from the GBM target. On this research a seco nd NP platform based the CNP shell itself was developed and displayed exce llent cytotoxic effect on GL261 murine GBM model under MHT stimulus.
\nFourth\, based on the PtBC \;mono mer developed in the first approach\, we developed bioinspired catechol-ba sed Pt(IV) free-standing membranes (FSMs) as conformable\, wet‑adhesive patches for insertion into resection cavities. This FSMs are formed by oxi dative co‑polymerization between a PtBC \;monomer a nd an amine co-monomer to yield malleable membranes that release Pt locall y. Physicochemical characterisation\, controlled-release assays and in vitro cytotoxicity against GBM lines demonstrated the FSM’s potent ial as a post-surgical local therapy with plausible ROS synergistic effect s.
\nAll in all\, this Thesis provides proof-of-concepts for multimodal treatments\, exploiting complementary me chanisms (DNA damage\, oxidative stress\, hyperthermia and sustained local delivery) to increase tumour selectivity and reduce systemic toxicity
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DTSTART:20251219T110000 DTEND:20251219T225959 LOCATION:ICN2 Seminar Room\, Campus UAB CATEGORIES:ICN2 Theses Defence END:VEVENT END:VCALENDAR