VALENTINA ALICE CAUDA

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Full Professor

Member of Interdepartmental Center (PolitoBIOMed Lab - Biomedical Engineering Lab)

+39 0110907389 / 7389 (DISAT)

Personal web site

Institute Institute of fundamental Physics and Materials for Nanotechnology
Research groups/teams MPMNT - Materials and Processes for Micro & Nano Technologies
Laboratories
Research projects

Funded by competitive calls

  • Current effective delivered dose monitoring for continuous renal replacement therapy , (2022-2022) - Responsabile Scientifico

    Corporate-funded and donor-funded research

    ERC sectors

    LS7_1 - Medical engineering and technology

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    I trattamenti di “continuous renal replacement therapy” (CRRT) sono frequentemente utilizzati in Terapia Intensiva per supportare la funzione renale di pazienti critici con danno renale acuto. In maniera analoga alla funzione renale fisiologica, l’eliminazione di soluti e sostanze di scarto attraverso una membrana da emodiafiltrazione è alla base del funzionamento di tali trattamenti. La quantità di depurazione che si desidera ottenere durante la CRRT identifica il concetto di “dose”, cioè la quantità di clearance che si desidera ottenere per un determinato soluto. La capacità dei soluti di oltrepassare la membrana ed essere eliminati all’interno dei fluidi di scarto, generati durante il processo depurativo, si riduce in maniera dinamica e imprevedibile a causa del “membrane fouling”. Il “sottotrattamento” involontario che ne consegue può avere degli effetti negativi sull’outcome del paziente, tanto che un attento e frequente monitoraggio della dose realmente erogata (“current effective delivered dose”) è raccomandato ma raramente applicato. Il presente progetto propone un sistema che ha la finalità di campionare i liquidi dal circuito extracorporeo e quantificare l’effettiva dose biologica somministrata durante il trattamento dialitico continuo. In particolare, si intende realizzare un campionamento automatico del materiale biologico, prelevato in maniera controllata, con una velocità ed un volume adeguato, dai siti di prelievo presenti nelle linee pre-filtro, post-filtro ed effluente. In particolare, si testeranno i flussi di aspirazione del sistema di prelievo al variare del flusso di sangue che scorre all’interno della macchina CRRT. Per valutare l’adeguatezza del sistema di campionamento si ricorrerà al calcolo dell’errore del bilancio di massa percentuale per un particolare soluto e si confronterà la massa di soluto in ingresso all’emodiafiltro (massa “pre-filtro”) con quella in uscita (massa “post-filtro” e massa “effluente”), così da validare il sistema di campionamento al fine di ottenere un bilancio di massa ottimale. L’obiettivo nel suo complesso è quello di realizzare e validare un sistema sia hardware sia software per il monitoraggio della dose effettiva dialitica a cui il paziente viene sottoposto durante un trattamento dialitico continuo durante il ricovero in terapia intensiva e in questo modo migliorare l’efficacia del trattamento CRRT.

    Departments

  • Multimodal Innovative THeranostic nanoSystem, (2022-2025) - Responsabile Scientifico

    Nationally funded research - PRIN

    ERC sectors

    PE4_4 - Surface science and nanostructures PE4_6 - Chemical physics PE4_11 - Physical chemistry of biological systems

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    Novel, smart, personalized early diagnosis and therapies are urgently needed to treat cancer, which still represents one of the major causes of death worldwide with an increasing trend. We propose to develop aMultimodal Innovative THeranostic nanoSystem (MITHoS) to cover the gap between the present anticancer nanomedicine tools and the clinical requirements. Despite the intense research development of nanotheranostictools, the deal with the complexity of these multi-component nanostructures in the biological environment is still an open challenge. Nanotheranostic agents, which act at the same time for therapy and diagnosis, are basedon the concerted actions of inorganic, organic and biological nanomaterials. Their effectiveness critically depends on the physico-chemical characteristics of their interfaces and on their behavior in physiological conditionsand biological environment. When considering drug delivery nanosystems or therapeutic nanoparticles activated by the action of external stimuli, there is currently scarce understanding and control of the fundamentalphysical, chemical and biological processes that are involved. This gap of knowledge has so far impaired the translation of research efforts towards in vivo testing and finally to clinical practice.MITHoS will be a hybrid theranostic nanosystem: an ultra-sound responsive core-shell nanoparticle, coupled to a pharmaceutically-relevant anticancer cargo, embedded in a cell-derived lipid bilayer shell and finallyequipped by targeting ligands. MITHoS will be validated against multiple myeloma, a tumor for which relapses and disease progressions are common among affected patients, owing to innate or acquired drug resistance. Itwill overcome the limitations of the current approaches with a bottom-up strategy: on the foundations of new, fundamental knowledge concerning nano/bio interfaces, we will build a finely tuned, multi-purpose andtime-controlled theranostic nanotool against cancer. We will use cutting-edge molecular simulation techniques to characterize all the involved nano/bio interfaces and develop predictive computational tools for the guidanceof the experimental investigations. At the same time, the experimental synthesis, characterization and test of the MITHoS nanosystem will evolve from simple, model systems to more complex nanostructures employing avariety of forefront techniques, from high resolution microscopy to X-ray and neutron scattering, until the final goal of in-vivo testing of the MITHoS system. Furthermore, novel methodologies for stimuli-responsive andremotely-controlled diagnosis and therapy will be developed.MITHoS concept will thus open new horizons in the nanomedicine field, proving how the synergic action of competences in the fields of physics, chemistry, material science, engineering, biophysics and biology can finallytranslate basic understanding into effective cancer treatment and overcome current barriers towards clinical translation.

    Departments

  • Sistema di monitoraggio e previsione della diuresi per il calcolo del rischio di insufficienza renale, e relativo metodo, (2021-2022) - Responsabile Scientifico

    Corporate-funded and donor-funded research

    ERC sectors

    PE6_7 - Artificial intelligence, intelligent systems, multi agent systems

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    Secondo dati recenti della American Society of Nephrology (ASN) e della European Renal Dialysis and Transplantation Association (ERA-EDTA), l’Insufficienza renale acuta (AKI) colpisce circa il 20% dei pazienti ospedalizzati e più del 50% dei malati critici in terapia intensiva. Un episodio di AKI aumenta la mortalità del paziente di 10 volte. Traducendo questi dati in termini economici, è possibile attribuire alla sindrome una spesa, derivante dai trattamenti medici (dialisi, cure farmacologiche, degenza ospedaliera, frequenti ri-ospedalizzazioni, sviluppo di comorbidità, etc.), che supera 1 B € annui a livello nazionale e di 15 B $ in USA. Il problema di questa patologia nei pazienti ospedalizzati risiede nell’assenza di sintomi evidenti precedenti la sua insorgenza. Ad oggi infatti non è possibile identificare un episodio di AKI prima che accada, limitandone così la prevenzione ed il trattamento. Per risolvere questo problema, la tecnologia oggetto di brevetto descrive un dispositivo medico innovativo che prevede gli episodi di AKI più di 24 ore prima della loro insorgenza. Combinando algoritmi di intelligenza artificiale con un innovativo sensore non-invasivo per il monitoraggio della diuresi, il sistema U-Care aiuta il medico a prevenire gli episodi di AKI, permettendo quindi al medico la modifica del percorso terapeutico per la prevenzione di tali episodi. Il sensore per il monitoraggio della diuresi possiede attualmente un TRL=5, e la sua accuratezza è stata validata in due ospedali italiani all’interno dei reparti di nefrologia e terapia intensiva. L’algoritmo di intelligenza artificiale per la predizione di episodi di AKI è stato invece allenato su più di 50.000 pazienti americani, e validato in modo retrospettivo su più di 9.000 pazienti europei, dimostrando un’alta sensibilità (82%) e specificità (82%). Il razionale del progetto proposto è la validazione su dati prospettici dell’accuratezza di modelli predittivi di episodi di Insufficienza Renale Acuta (Stage 2 e 3 KDIGO) in pazienti durante la degenza in reparti di terapia intensiva, attraverso lo svolgimento di uno studio clinico pilota osservazionale multi-centrico.

    Departments

  • A KEY TO THE UNDERSTANDING OF EXTRACELLULAR VESICLES AND RATIONAL DESIGN OF MIMICKING NANOPARTICLES , (2021-2025) - Responsabile Scientifico

    UE-funded research - H2020 - Excellent Science - FET

    ERC sectors

    LS7_1 - Medical engineering and technology LS1_11 - Biochemistry and molecular mechanisms of signal transduction LS1_6 - Lipid synthesis, modification and turnover LS1_8 - Biophysics (e.g. transport mechanisms, bioenergetics, fluorescence) LS1_1 - Molecular interactions

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    Extracellular vesicles (EVs) are nowadays well known as small vesicles (< 1µm) produced by almost all cell types, ensuring efficient communication among cells throughout the body, by transporting molecules and nucleic acids. Actually, they contain cell-type specific signatures and have been proposed as biomarkers in a variety of diseases. Therefore, the species exposed at the external surface or incorporated in the lumen have a strategic importance for EV biological functions; however, their role and related functions are still not entirely clear and are topic of current research. With the MIMIC-KeY project we propose a radical change of paradigm to understand and predict the behaviour of natural EVs and then design and produce synthetic EV-mimicking nanoparticles.

    Departments

  • Fighting cancer relapse with remote activation of smart and targeted nanoconstructs (XtraUS), (2021-2022) - Responsabile Scientifico

    UE-funded research - H2020 - Excellent Science - ERC

    View project record on CORDIS

    ERC sectors

    LS7_3 - Pharmacology, pharmacogenomics, drug discovery and design, drug therapy LS7_1 - Medical engineering and technology

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    This project XtraUS focuses on the prevention of cancer relapse and on the achievement of an early cure of recurrence, thus having a heavy impact on health and on its financial implications. Actually, many patients unfortunately get into a recurrence of their primary tumor disease, since their cancer is not fully remitted and they require further treatment to manage it. Minimal residual disease (MRD) after potentially curative treatment generally contributes to disease relapse and is the target of early adjuvant treatments. In particular, circulating tumor cells (CTCs) in the blood stream have a key role in cancer progression, recurrence and metastasis spreading. However, their such tiny amount is difficult to detect by conventional laboratory tests. From a social and financial perspective, fighting these cancer cells has a huge impact on cancer relapse prevention and thus on the health, quality of life and overall cancer treatment expenditure.XtraUS aims at validating a breakthrough technology to fight CTCs in the bloodstream and thus reduces the rise of MRD and further cancer relapse. It applies an extracorporeal blood circulation set-up exploiting a novel stimuli-responsive, targeted and non-immunogenic nanoconstruct, remotely activated against CTCs. XtraUS results in a personalized and translational approach, with high-target specificity and reduced collateral damage to both blood and adjacent healthy tissues. With this technology, we aim to advance the conventional treatments of CTCs in the blood stream, proposing a more effective and safer treatment to fight cancer relapse and metastasis spreading than the current ones. The driving idea is to render permanent and efficacious the first treatment offered to patients for their primary tumor disease, avoid cancer relapse, and reduce all associated costs.XtraUS is a versatile technology, with potential applications also on many other diseases, with huge societal and economic impacts on public health.

    Departments

  • Composizione farmacologica per massimizzare l’efficacia terapeutica degli inibitori del proteasoma, (2020-2021) - Responsabile Scientifico

    Corporate-funded and donor-funded research

    ERC sectors

    LS7_3 - Pharmacology, pharmacogenomics, drug discovery and design, drug therapy

    SDG

    Obiettivo 3. Assicurare la salute e il benessere per tutti e per tutte le età

    Abstract

    Gli inibitori del proteasoma (IP) sono ampiamente utilizzati per il trattamento del mieloma multiplo (MM) e del linfoma mantellare (MCL). Tuttavia, le ricadute, la resistenza innata e le progressioni della malattia sono frequenti nei pazienti di MM. Recentemente, è stata proposta una nuova combinazione sinergica, in grado di aumentare l’efficacia degli IP, in particolare contro MM, MCL e linfoma di Burkitt (BL). La letalità sintetica (LS) è l’interazione tra due geni coessenziali la cui singola inibizione mantiene la cellula in vita, ma la cui inibizione congiunta produce morte cellulare. Il fenomeno di LS è già sfruttato clinicamente, ma la sua efficacia è limitata dalla ridotta biodisponibilità e dall’idrofobicità delle molecole usate. Gli autori hanno recentemente rivestito nanoparticelle (NP) di silici mesoporose (SM) con doppi strati fosfolipidici (DSL) di origine commerciale e artificiale, dando origine a innovative vescicole liposomali (chiamate anche “protocells”) ingegnerizzate per il drug delivery intracellulare e dotate di agenti di targeting. Tali NP possono diventare “proiettili di LS” capaci di incorporare agenti antitumorali e di targeting con un’elevata efficienza di rilascio. Tali nanocostrutti SM@DSL permettono il trasporto efficiente senza off-target e perdite incontrollate di farmaco, la concentrazione del/dei farmaco/i all’interno del nanocostrutto e il rilascio controllato intracellulare di tali farmaci. Infine, possono essere equipaggiati con anticorpi monoclonali (mAb) per un targeting efficace delle cellule bersaglio. Lo sviluppo di tale tecnologia soddisfa i seguenti bisogni:- massimizzare l’efficacia di LS con una formulazione farmacologica veicolata da SM@DSL-mAb, superando le attuali limitazioni dei farmaci utilizzati e aumentandone la selettività - recuperare il farmaco AGI-6780, già approvato ma escluso dalla traslazione clinica per bassa biodistribuzione- migliorare le cure contro il cancro

    Countries

    • ITALIA

    Departments

  • Multifunctional Immunocompatible NanoTheranostics to modulate tumor microenvironment and improve treatment monitoring: A double blow to pancreatic cancer, (2019-2021) - Responsabile Scientifico

    UE-funded research - H2020 - Excellent Science - Marie Curie

    View project record on CORDIS

    Abstract

    Different nanomaterials were developed so far in particular against cancer, paid very little attention to their potential immunogenicity, to their final destiny, as well as to the importance of zero-delivery in unwanted places. Thus, there is still a huge disproportion between the present nanomedicine tools and the clinical requirements. The ambitious purpose of the MINT project is to develop immunocompatible tumor targeted zinc oxide nanocrystals (ZnO-NCs) coated by extracellular vesicles (EVs) with enhanced drug delivery capabilities to cancer cells, by disturbing the supportive tumor microenvironment of pancreatic cancer, one of the most lethal human malignancies. Moreover, ZnO-NCs is doped with transition metal elements to be probed for treatment monitoring.In recent years while several therapeutic advances were implemented in many cancer types, the scenario of pancreatic cancer remains unchanged. The main factor behind the limited efficacy of chemotherapeutics in pancreatic cancer is its complex microenvironment. We propose to deliver Hedgehog pathway inhibitor & vascular endothelial growth factor receptor kinase inhibitor simultaneously through the multifunctional EV-coated doped ZnO-NCs to deplete tumor stroma, normalize tumor vascularity and improve pancreatic cancer therapeutic index. The proposed Fellowship will enable a highly interdisciplinary collaboration between the Researcher, experienced in targeted therapy & pancreatic cancer biology, and the supervisor, pioneer in designing nanotheranostics. These working conditions will effectively promote the Researchers professional development, providing her with excellent new expertise in nanotheranostics and fundamental leadership skills, significantly widening her career perspectives. The project outcomes will be of tremendous benefit to the European biomedical sectors, bridge the current gap between the conventional therapies and the Frontier research in the field of cancer nanomedicine.

    Countries

    • ITALIA

    Departments

  • TROJANANOHORSE - Hybrid immune-eluding nanocrystals as smart and active theranostic weapons againstcancer, (2016-2021) - Responsabile Scientifico

    UE-funded research - H2020 - Excellent Science - ERC

    View project record on CORDIS

    Abstract

    Nanomedicine tools for cancer treatment comprise many nanosized systems, so far developed with smart functions such as efficient drug delivery and cell targeting abilities. However they remain still under-characterized in terms of immunogenicity, potential toxicity due to the materials itself or the unwanted release of drugs. To overcome these challenges this project aims to develop a new generation of multifunctional therapeutic and diagnostic (thus theranostics) nanosystems displaying non-immunogenicity, improved cancer treatment, cell imaging, and high safety for the hosting organism. The innovative concept behind this approach relies on a TrojaNanoHorse (TNH) system, here validated against leukaemia. The injectable TNH have a biomimetic non-immunogenic shell. Studies will show the intrinsic therapeutic activity of the nanocrystalline core for cancer killing, without the use of chemotherapeutic drugs, and its light emission. The hemocompatibility, anti-thrombogenicity, and targeting ability toward malignant blood cells will be proved during this project. The whole TNH would go beyond the state-of-the-art due to its biomimetic shell, absence of drugs, its safety and biodegrading fate, and light emissions for diagnosis. This project will also develop novel set-up for based therapy and diagnosis, impacting on future technology, new standardized protocols for nanomaterial safety assessment, and study chemical and biological mechanism of cancer cell killing. Achieving the ultimate goal of a multifunctional TNH will require multidisciplinary expertise in chemistry, material science, biology, medicine and engineering, opening new horizons as nanomedicine tools for efficient cancer therapy with strong scientific, technological and socio-economic benefits.

    Countries

    • BELGIO
    • ITALIA

    Departments

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Funded by commercial contracts

  • Accordo ex art. 15 L. 241/90 tra Politecnico di Torino - DISAT e Azienda Ospedaliera Santa Maria di Terni , (2019-2023) - Responsabile contrattuale

    Departmental agreements

    Countries

    • ITALIA

    Institutes/Companies

    • Azienda Ospedaliera Santa Maria
  • Sviluppo di algoritmi di AI per la predizione di insorgenza di insufficienza renale acuta, (2020-2021) - Responsabile Scientifico

    Commercial Research

    Countries

    • ITALIA

    Institutes/Companies

    • NOVASIS INNOVAZIONE SRL

    Departments