Research Lines in the Polymer Therapeutics Laboratory

Currently Funded Projects

Polymer Therapeutics for pediatric solid tumors (PT4PST)

FUNDING AGENCY: AECC (Ayuda Investigador Talento AECC 2021)

PRINCIPAL INVESTIGATOR: Dr. Inmaculada Conejos-Sánchez

 

Beca Santiago Grisolía

FUNDING AGENCY: Conselleria d’educació. Generalitat Valenciana (CIGRIS/2021/100)

PRINCIPAL INVESTIGATOR: Dr. M. J. Vicent.

New Nanotechnological therapy for Parkinson’s disease: Nose to brain delivery of GBA-polymer nanoonjugtes

FUNDING AGENCY: Health Foundation La Caixa.

Coordinator: M Martínez-Vicent (VHIR, Bareclona), PI: MJ Vicent, J Lorenzo

 

MULTISMART-Multi-component Soft Materials Advanced Research Training Network.

Coordinator André Del Guerzo (univ Bordeaux, France). (MJVicent Partner at CIPF).

 

POLYBRAINT-Versatile Polypeptide-based Intranasal Drug Delivery Platform(s) to Tackle CNS Disorders

FUNDING AGENCY: ERC-2022-PoC-101069391.

LENGTH: 01/04/2022 to 30/11/2023

PRINCIPAL INVESTIGATOR: Dr. María J. Vicent.

Research for a new Vaccine for Human respiratory Disease

HIPRA and PTS SL

Research and Development Contract

New Therapeutic approaches to Achondroplasia

FUNDING: Marató TV3.

PRINCIPAL INVESTIGATOR

M. Angela Nieto.

Dr María J. Vicent as team member

Diseño de sistemas poliméricos teragnósticos para el tratamiento de cáncer de mama

FUNDING: Generalitat Valenciana

PRINCIPAL INVESTIGATORS

M. Medel

Synergistic Approach for Metastatic Tumor and Neurodegenerative Disorder Treatments using Versatile PolyPeptide-based Conjugates

FUNDING: MICINN Plan Nacional I+D 2019

PRINCIPAL INVESTIGATOR

MJ. Vicent

 

BIOMOLMACS: Molecular Machines Functioning in Cells

Funding Agency: H2020-MSCA-ITN-2019

PRINCIPAL INVESTIGATORS:

Coordinated by Dr Remzi Bezer (Univ. Warwick, UK).

Partners: Prof. Ben Feringa (Univ Groningen, TUE), Prof Jan van Hest (Eindhoven Univ Technology, NL), Dr María J. Vicent (CIPF, SP), Prof Sebastien Lecommandoux (Univ Bordeaux, FR), Prof. David Leigh (University of Manchester), Prof. Petra Schwille (Max-Planck-Institute of Biochemistry MAXP, DE) , Prof. Robin Sgattock (Imperial College London ICL, UK), Prof. Wolfgang MEIER (University of Basel UBAS, SW) ,Prof. Richard Hoogenboom (Avroxa BVBA AVR, BL)  Dr. Vicent J. Nebot (Polypeptide Therapeutic Solutions SL, Dr. Henk Janssen (SyMO Chem SyMO, NL).

Associated partner:   Polymun Scientific Immunbiologische Forschung GmbH, Austria Dr. Andreas Wagner

The main motivation of BIOMOLMACS training network is to establish a multidisciplinary training network on the emerging topic of molecular machines and to train the next generation of highly skilled researchers in this exciting field. In the last decade, great efforts have been spent on the development of synthetic strategies for the creation of molecular machines, and these efforts have been acknowledged by the Nobel committee in 2016. In parallel, synthetic and polymer chemistry fields have made significant advances in the last decade, to the point that we are able to design and control the sequence of individual repeat units along synthetic macromolecules. Sequence controlled polymers open up greater possibilities in the precise formation of nanoparticles such as polymersomes, and even support the new generation of artificial cells. The synthetic combination of molecular machines and precisely designed synthetic macromolecules will open new avenues for innovative nanobiomedicinal applications. Early Stage Researchers of BIOMOLMACS will be trained on the design, chemical synthesis, and biophysical characterization of such complex macromolecular architectures as well as their incorporation in artificial and living cells. Finally, biophysical understanding of the molecular interactions in living/synthetic systems will be able to bridge the gap between fundamental and applied research in this exciting field.

Design of Transport Systems for Intranasal Drugs as a Nanotechnological Platform for the Treatment of Amyloidosis in the Central Nervous System

FUNDING AGENCY: Generalitat Valenciana.

PRINCIPAL INVESTIGATORS: I. Conejos-Sanchez

The growing incidence of neurodegenerative disorders in an ageing population in parallel with the prevalence of palliative treatments, reveal the unmet need for novel approaches to limit brain-related disease progression. Alzheimer’s Disease (AD) is one of the largest public health challenges faced in terms of costs and special medical care. The bottleneck to central nervous system (CNS) therapies is crossing the Blood Brain Barrier (BBB). Our project seeks to provide a novel CNS delivery platform for restorative therapy in neurodegenerative disorders by nanotechnological means – the combination of nanomedicine and Polymer Therapeutics (PT), with already shown clinical benefits. Our approach is based in novel well-defined biodegradable architectures prepared via controlled polymerization, bioresponsive linkers, and crosslinking together with thorough physico-chemical characterization. Engineered conjugates produced using iterative optimization based on structure-activity relationships determined in well-defined biological models will enable the identification of lead candidates. Additionally, polymeric nanosystem multivalency will allow us to create combination therapy targeting inflammatory and oxidation pathways to trigger neuroprotective/neuroregenerative mechanisms. This is an innovation in the field, through the simultaneous inclusion of active biomolecules which will allow us to construct a theranogstic and targeted therapy with synergistic properties. Also, we are exploring the administration of this novel therapy by the intranasal (IN) route, an innovative approach within the PT field. We are constructing non-invasive, safe, controlled, and reliable multifunctional nanosystems for drug delivery and disease monitoring for applications in AD. Later on, this technology can be extrapolated to other CNS pathologies where neuroinflammation and neurodegeneration are features.

RabTEN: Study of the Role of the RAb11a GTPase in Prostate Cancer for its Use as a Biomarker

FUNDING AGENCY: Generalitat Valenciana

PRINCIPAL INVESTIGATORS: Ana Armiñán

Prostate cancer (PCa) is the first common cancer in men leading to 10% of cancer deaths, mainly as consequence of castration-resistant PCa (CRPC). Currently, there are very few biomarkers that have been incorporated in the routine clinical management of PCa; however, large-scale studies have discovered different molecular biotypes, suggesting that clinical heterogeneity in patients is a consequence of the molecular heterogeneity in cancer genomes. This is particularly relevant for phenotypes which vary in outcome and therapeutic responsiveness. PTEN is a tumor suppressor gene deactivated in a wide variety of tumors, including PCa, making it an interesting candidate for the application of personalized therapies in combination with other biomarkers. In addition, studies have indicated a role for GTPases in the regulation of PTEN activity. Rab GTPases are classical regulators of intracellular trafficking and key roles in control of tumor progression and metastasis have recently emerged. Hence, Rab GTPases can be considered as targets for the development of new therapies. Preliminary studies performed in the Polymer Theraputics group at the CIPF have demonstrated a relation between PCa progression and Rab11a expression. RabTEN will gain a deeper understanding of the role of Rab11a in PCa, including the possible regulation of PTEN and the mechanisms responsible for the emergence of CRPC, which may allow better stratification of PCa patients. Furthermore, RabTEN will also elucidate the contribution of Rab11a GTPase to the regulation of exosomal cargo packaging and extracellular release, given the importance of these processes to cancer. POLYMMUNE: Off-the-Shelf Polypeptide-based Immunotherapy for Advanced Melanoma Treatment.

POLYMMUNE: Off-the-Shelf Polypeptide-based Immunotherapy for Advanced Melanoma Treatment.

FUNDING AGENCY: ERC-2018-PoC

PRINCIPAL INVESTIGATORS: Dr María J. Vicent (CIPF, SP) Collaborators: Prof Helena Florindo (UNiv Lisbone, PT)

Despite various existing drug delivery methods, the key challenge remains: how to deliver drugs to the desired site of therapeutic action to achieve best treatment outcome, while minimizing side effects? This is even more challenging in cancer immunotherapy as a complex interplay of immune reactions need to be activated. POLYMMUNE will evaluate the technical and commercial viability of our novel polymeric nanocarrier platform (developed during my ERC Consolidator grant MyNano) for targeted drug delivery of a wide variety of diseases and therapeutics. As proof of concept, we will focus on immunotherapy delivery for metastatic melanoma. Globally ~132,000 new melanoma cases will be diagnosed each year and despite recent successes, only 50% of the patients respond to novel immunotherapies that are costly, while causing severe side effects. Coupling a commercially available antigen (Melan-A) against metastatic melanoma to our nanocarrier will activate a broad immune response, resulting in an effective cancer vaccine that potentially targets different melanoma types, enabling off-the-shelf production. This dual action will lead to increased clinical benefit, which will come with less side effects and will be 5-10-fold cheaper than current treatments. Additionally, our conjugate is industrially scalable and thus overcome a major bottle neck of current nanocarrier-based medicine. We envision our platform technology to be used as a method of choice for drug delivery in many medical applications, such as cancer immunotherapy and neurodegenerative diseases. These applications are within reach, as depending on the modification, our conjugates can e.g. bypass the blood brain barrier and potentially be administered intranasally (nanogel). Our platform offers a highly attractive business case, as biotechnology and pharmaceutical companies heavily invest in nanoconjugates due to the need for novel drug delivery strategies.

EU-OPENSCREEN-DRIVE: Ensuring long-term sustainability of excellence in chemical biology within Europe and beyond

FUNDING AGENCY: H2020-INFRADEV-03-2018-2019

PRINCIPAL INVESTIGATORS: Coordinated by Philip Gribbon (Univ. Berlin, Germany), Dr María J. Vicent partner at CIPF. Project with EU-OPENScreen Partners

EU-OPENSCREEN ERIC (EU-OS), the European Research Infrastructure Consortium for Chemical Biology, provides access to a distributed network of national screening and chemistry facilities, a common database, and a central headquarter that manages the joint compound collection and coordinates project flow and training. EU-OPENSCREEN-DRIVE will ensure long-term sustainability of EU-OS operations by promoting measures for i) widening awareness of academia and industry for its services and data, ii) growing capacity and competence in its field across Europe, and iii) completing the management processes needed for a large distributed infrastructure. EU-OS provides world-class services to academia and industry in the fields of small molecule screening and medicinal chemistry. Thereby, it promotes the rich chemical knowledge of Europe and enables systematic studies of the bioactivities of a larger collection of compounds leading to ground-breaking insights into cellular and organismal metabolic or signalling pathways. After careful consideration of IPR from all stakeholders involved, all results will eventually become available to the public. EU-OS will thereby also play an increasingly important role in facilitating the drug discovery process in Europe. In addition, it also has a great potential for innovative development of biomarkers and other diagnostics. EU-OS-DRIVE will further help the EU-OS-ERIC to deliver its added-value via constant re-use of generated data and tools by users across the globe and to support the competitiveness of European life science industries. EU-OS developed its concept and business plan during the preparatory phase and has received information on the Commission Implementing Decision on setting up the EU-OS European Research Infrastructure Consortium (EU-OS-ERIC) in March 2018. In 2018, EU-OS started its ERIC operations with seven founding members and one observer. Since 2019, EU-OS counts 8 member countries.

Development of Topical Therapies Based on Polypeptide Delivery systems: PolyPepSkin

FUNDING AGENCY: RETOS investigación. MICINN.

Coordinator: Polypeptide Therapeutic Solutions SL., Partners: Dr María J. Vicent partner at CIPF, Prof Beatriu Escuder (UJI, SP)

El objetivo del presente Proyecto es desarrollar un nuevo producto para el tratamiento tópico de afecciones inflamatorias de la piel basado en un hidrogel formado por co-polímeros reticulados polisacárido (PSC)-poliaminoácido (o polipéptido, PAA) soportados por redes fibrilares autoensambladas combinado con fármacos anti-inflamatorios vehiculizados mediante sistemas de transporte polipeptídicos. La administración tópica de medicamentos directamente en la piel ofrece un enfoque para el tratamiento específico de afecciones dermatológicas y otras enfermedades localizadas a la vez que se reduce el riesgo de efectos secundarios sistémicos. Sin embargo, la piel está estructurada específicamente para proteger el cuerpo actuando como una barrera a la permeación de sustancias exógenas. A pesar del creciente interés en el desarrollo de terapias eficaces para el tratamiento de enfermedades de la piel, en concreto la psoriasis, prácticamente todos los esfuerzos en desarrollo de terapias que han alcanzado el mercado se han dirigido de forma casi exclusiva nuevos principios activos, dianas terapéuticas o terapias de combinación que acaban siendo formulados utilizando ingredientes y excipientes convencionales. El uso de polímeros biodegradables representa una mejora respecto a las alternativas convencionales (microporación, electroporación, microagujas, etc.) para administración tópica de principios activos debido en primer lugar, a su ruptura en fragmentos biocompatibles que pueden ser metabolizados y eliminados de forma natural por el cuerpo.1 El uso de polipéptidos tiene beneficios debido a su biodegradabilidad, biocompatibilidad y también a que son capaces de mejorar la biodisponibilidad del fármaco. Los aminoácidos (bloques de construcción de nuestros polipéptidos) y sus derivados, son moléculas que aportan diversos beneficios en el cuidado de la piel. Además, se ha reportado que son capaces por ellos mismos de interaccionar de diversas formas con el estrato córneo y promoviendo la permeación transdérmica de los propios aminoácidos y activos aplicados en combinación.2-4 Nuestra propuesta para abordar este desafío es el desarrollo de nanomedicinas, nuevos sistemas de administración de fármacos como terapias tópicas para mejorar la penetración del principio activo. Para ello, proponemos el uso de sistemas MultiMateriales Hidrogel-Nanomedicina como una aproximación integral al desarrollo de un Producto Seguro y Eficaz para el tratamiento de enfermedades de carácter inflamatorio en piel, en concreto en este proyecto se abordará la psoriasis

Development of a Platform of Gene Therapy for Genetic Renal Diseases

FUNDING AGENCY: RETOS investigación. MICINN.

Coordinator: ViralGen Vector Core SL., Partners: Dr M.J. Vicent partner at CIPF; Prof Gloria González and Rafael Aldabe (Fundacion para la investigacion medica aplicada, CIMA); Polypeptide Therapeutic Solutions sl; Universidad Carlos III de Madrid

Adeno-associated viruses (AAVs) are non-enveloped viruses that constitute one of the most actively investigated gene therapy vehicles. AVV particles can be engineered to deliver nucleic acids of therapeutic interest to target cells since tissue-specific tropism is determined by capsid sequence. AAVs have been shown to be safe and effective in clinical studies, and recently, Glybera®, the first AAV based vector for gene therapy, has entered the market. The project aims to evaluate the applicability of AAV variants for the treatment of two renal diseases: autosomal dominant polycystic kidney disease type II (ADPKD II) and Denys–Drash syndrome (DDS). Kidney diseases are ideally suited for gene therapy treatment as kidney is a highly vascularized organ potentially allowing an easy access of the therapeutic vectors to all cells. In order to promote kidneys tropism, a versatile and simple methodology for the preparation of welldefined AAVs-polyglutamate nanocarriers can be designed by the modification of the surface of the viral capsids. In this case the surface will be functionalized with poly glutamic acid (PGA) polymers. The carboxylated polymers exhibit renal targeting properties, therefore PGA based-polypeptides could be used as a renal targeting carrier for therapeutic agents. In addition, PGAs can also be post-polymerization controlled modified with targeting moieties, such as folate and peptides (RGD, Galectin-3 and others), to further increase renal targeting capacity. A library of modified AAVs will be generated using PGA of different molecular weight and bearing different targeting agent. The capacity of the viral vectors to transfect renal cells will be evaluated in vitro and the best candidate will be finally testesd in animal models

Combinatorial Treatment of Neural Precursors and a Novel Nanoconjugate of Fasudil for Clinical Applications in Spinal Cord Injury

FUNDING AGENCY: Marató TV3.

PRINCIPAL INVESTIGATORS: DR Ferran Pellicé (Vall d'Hebron Hospital), Dr María J. Vicent partner at CIPF with Dr Victoria Moreno

While recent decades have brought significant improvements in rescuing neuronal activity after spinal cord injury (SCI) at pre-clinical phases, translation to the clinic remains inefficient. The complexity of SCI, involving cascades of concatenated extrinsic and intrinsic events, requires rapid intervention with a combination of therapeutic strategies. Stem cell transplantation can create a permissive environment for neuronal survival; however, limited spontaneous regeneration of axonal tracts necessitates additional support. Our robust pre-clinical data regarding SCI treatment has demonstrated an efficient combination of neuronal precursor cells, derived from the spinal cord tissue (epSPCs), and the local administration of a new Fasudil nanoconjugate (PGA-SS-FAS), which allows the controlled and sustained release of a Rock kinase inhibitor. Previous results demonstrated that this combination can rescue voluntary motor tasks, promotes neuronal neuroprotection, and enhances regeneration by reducing glial scar formation. Herein, we propose to translate this combination treatment into clinical practice by generating a cell bank of human neural precursor cells from fetal tissue under Good Manufacturing Practice (GMP) conditions and manufacturing clinical grade PGA-SS-FAS at a large scale following the requirements specified by the national medicines agency to be registered as clinical research medicines (AEMPS). The final goal of this proposal is to move towards a pilot Phase I clinical trial for acute SCI, including the clinical trial design from the final users at the safety and efficacy evaluation stages. The consortium for this proposal is represented by interdisciplinary specialists with complementary expertise in cell biology, chemistry, neurology, neurosurgery, spinal surgery, and neurorehabilitation.

PREMICAT-DHA: Hybrid Strategy based on Catheterization and the Polymeric Conjugation of Docosahexaenoic acid for the Prevention of Myocardial Damage Induced be Reperfusion

FUNDING AGENCY: ISCIII. DTS2017/00067.

PRINCIPAL INVESTIGATOR: Dr P. Sepúlveda (IISLAFe) , Dr María J. Vicent (CIPF)

Acute myocardial infarction (AMI), even after reperfusion, leads to a significant loss of cardiomyocytes and to a tissue deterioration process known as ventricular remodeling. The best therapy to minimize the effects of infarction is coronary angioplasty, a procedure performed by cardiologist hemodynamist consisting of the introduction of a catheter with a balloon that swells once placed in the area of the obstructed coronary artery and reestablishes the coronary flow. However, interventional therapy has limitations, such as the risks of restenosis, the limited time frame in which treatment is effective and, above all, reperfusion injury. The sudden entry of blood after opening the catheter through the occluded artery generates an oxidizing and inflammatory cardiac environment that can adversely affect cell function and survival. Administration of drugs or growth factors to cardiac ischemic tissue has been found to contribute positively to tissue repair by reducing apoptosis and increasing cardiomyocyte regeneration. However, these should be administered in the area of the lesion and not by systemic route. Our project is committed to assess the feasibility, safety and efficacy of a two-stage hybrid therapy in which we combine the use of a newly generated cardiac stent designed and validated through a Health Technology Development Project previously granted to this consortium (DTS15 / 0079) for intracoronary administration with a potent pro-resolutive molecule derived from omega-3 fatty acids, docosahexaenoic acid (DHA) lipidic mediator, covalently conjugated to polyglutamic acid (PGA) in a synthesis process based on polymer therapeutics, which was also generated and validated in the previously mentioned coordinated project (DTS15 / 0083). In order to obtain solid results, we propose a comprehensive approach, which, if demonstrated clinically effective, will be applicable to a significant proportion of the population affected by AMI.

Polymer Therapeutics Design to Cross the Blood–brain Barrier in the Treatment of Neurodegenerative Disorders – Exploring the Intranasal Route

FUNDING AGENCY: Plan Nacional I+D. Ref. SAF2016-80427-R. MINECO.

 PRINCIPAL INVESTIGATOR: Dr M. J. Vicent

The growing incidence of neurodegenerative disorders in an ageing population in parallel with the prevalence of palliative treatments, reveal the unmet need for novel approaches to limit brain-related disease progression. Alzheimer’s Disease (AD) is one of the largest public health challenges faced in terms of costs and special medical care. The bottleneck to central nervous system (CNS) therapies is crossing the Blood Brain Barrier (BBB). This project seeks to provide a novel CNS delivery platform for restorative therapy in neurodegenerative disorders by nanotechnological means – the combination of nanomedicine and Polymer Therapeutics (PT) with already shown clinical benefits. Our approach is based in novel well-defined biodegradable architectures prepared via controlled polymerization, bioresponsive linkers, and crosslinking together with thorough physico-chemical characterization. Engineered conjugates produced using iterative optimization based on structure-activity relationships determined in well-defined biological models will enable the identification of lead candidates. Additionally, polymeric nanosystem multivalency will allow us to create combination therapy targeting inflammatory and oxidation pathways to trigger neuroprotective/neuroregenerative mechanisms. This is an innovation in the field, through the simultaneous inclusion of active biomolecules which will allow us to construct a theranogstic and targeted therapy with synergistic properties.

BIOChiP: Identification of Molecular Biotypes of Prostate Cancer as a Base for Precision Medicine

FUNDING AGENCY: Generalitat Valenciana. Ayudas I+D Para Grupos De Investigación De Excelencia

Coordinator: Dr J.A. López-Guerrero (FIVO), M.J. Vicent partner at CIPF and Antonio Pineda-Lucena (IISLaFe)

El cáncer de próstata (CaP) es el segundo tumor en incidencia en hombres y la sexta causa de muerte por cáncer en países desarrollados. Existe una gran diferencia en cuanto a incidencia entre países desarrollados y paises en desarrollo, fundamentalmente debido a la disposición en los primeros de procedimientos que los hacen más fácilmente detectables. Sin embargo, llama la atención que la tasa de mortalidad es similar en los dos contextos, lo que nos indica que en nuestro entorno se está llevando a cabo un sobrediagnóstico de CaP con un posible comportamiento indolente y un sobretratamiento con el consiguiente impacto sociosanitario que ello supone. En el contexto diagnóstico nos encontramos fundamentalente con dos retos: en primer lugar, mejorar la especificidad del diagnóstico del CaP; y en segundo lugar, identificar aquellas formas con un comportamiento más agresivo que requieran de tratamiento más radicales, de aquellos con un comportamiento indolente que pudieran beneficiarse de estrategias más conservadoras como la vigilancia activa. Por otra parte, en el contexto del tumor en fase avanzadas, CaP resistente a castración (CPRC), requerimos de tratamiento más eficaces que mejoren las espectativas de los tratamientos convencionales. Paralelamente, la revolución biotecnológica de los últimos años, con técnicas como las –ómicas y la secuenciación de nueva generación o NGS (Next Generation Sequencing), junto con los nuevos conocimientos de la biología del cáncer, han cambiado el concepto que teníamos del CaP y hemos pasado de tener una enfermedad pobremente entendida y heterogénea desde el punto de vista clínico a una colección de subtipos homogéneos identificables por criterios moleculares. En este sentido, y al igual que sucede en otras neoplasias como las leucemias, los linfomas, o el cáncer de mama, pensamos que la clasificación molecular del CaP constituirá un paso crítico y fundamental tanto en el desarrollo de biomarcadores que diferencien formas agresivas e indolentes de la enfermedad como el desarrollo de terapias dirigidas a determinados biotipos tumorales. El pryecto BIOChiP lo presentamos un equipo multidisciplinar de investigadores con un alto componente traslacional y orientados a optimizar el manejo clínico del paciente con CaP de forma racional en base a criterios moleculares. De ahí que planteamos la propuesta en dos escenarios. En enfermedad localizada, donde buscamos encontrar biomarcadores cáncer específicos y asociados al grado de agresividad tumoral, que nos sirvan de base para diseñar y proponer un programa de cribado en población de riesgo, y un programa de vigilancia activa en el que se evalúen biomarcadores asociados al riesgo de progresión. En enfermedad avanzada, y en base a la experiencia previa del grupo investigador, perseguimos optimizar el tratamiento del CPRC en base del perfil molecular del tumor y la sensibilidad de cada biotipo tumoral a determinados fármacos, con el fin de diseñar un compuesto basado en la nanomedicina que permita tratar un subtipo de CaP de forma más eficaz y segura para el paciente. En este contexto, se prevé adquirir la suficiente evidencia preclínica como para diseñar y proponer un ensayo en Fase I/II.

MyNano: Designing Personalised Polymer-based Combination Nanomedicines for Advanced Stage Cancer Patients.

FUNDING AGENCY: ERC Consolidator Grant 2014

PRINCIPAL INVESTIGATOR: M. J. Vicent.

Research on anti-cancer therapies has provided little progress towards improved survival rates for patients with metastatic disease. The intrinsic advantages of polymer conjugates can be optimized to rationally design targeted combination therapies, a concept I (Maria Jesus Vicent) pioneered that allows for enhanced therapeutic efficiency. Early clinical trials involving conjugates proved activity in chemotherapy refractory patients and reduced drug-related toxicity. However, there is a growing concern about patient variability regarding tumor patho-physiology that underlies successful therapeutic outcome. Specific biomarkers are required to select those patients most likely to show good clinical response to these therapies. The objective of MyNano is to engineer polymer-based combination therapies designed to treat metastatic breast cancer in a patient personalized manner. Therefore, novel multicomponent polymer conjugates with precise control over size, shape, solution conformation, multifunctionality, and bioresponsiveness will be obtained, while in parallel their structure activity relationships to underlying proposed mechanisms of action in clinically relevant models will be studied. Polyglutamates obtained by controlled polymerization and self-assembly strategies will be the carriers. Primary breast cancer patient tissue will be used to generate cell and in vivo models representing different clinical molecular subtypes. MyNano will also investigate new combination strategies using current treatments together with inhibitors of tumor-derived exosome release pathways, phenomenon related to metastasis and resistance mechanisms. The aim is to provide a novel methodological approach that would allow by reiterative design to optimize the design of the next generation nanoconjugates for the treatment of specific metastatic cancer clinical subtypes. MyNano will be a breakthrough as it introduces a paradigm shift in the strategy to design nanomedicines in areas of unmet clinical need.

Identificación de Nuevos Biomarcadores y Desarrollo de Conjugados Poliméricos de Combinación en Cáncer de Próstata Metastásico

Funding Agency: ASEICA 

PRINCIPAL INVESTIGATOR: M. J. Vicent

El Cáncer de Próstata (CaP) es un tumor multifocal y molecularmente heterogéneo lo que dificulta su diagnóstico y caracterización pronóstica. Los métodos convencionales empleados en el diagnóstico del CaP llevan asociados un elevado riesgo de sobrediagnóstico y sobretratamiento, lo que representa un impacto de primera magnitud en Salud Pública. Esta heterogeneidad molecular subraya la presencia de distintas entidades moleculares que definen biotipos tumorales específicos que podrían beneficiarse de un manejo clínico de más precisión, incluyendo el diseño y las estrategias terapéuticas más adecuadas. En este sentido en este proyecto se determinarán perfiles metabólicos específicos de la enfermedad que nos permitan detectar nuevos biomarcadores ayudando de este modo a evitar el sobrediagnóstico y consecuentemente el sobretratamiento del CaP. Por otro lado, cabe destacar que, a pesar de estos avances terapéuticos, el CPRC sigue siendo una enfermedad con baja tasa de supervivencia. Entre las terapias dirigidas cabe destacar el empleo de inhibidores de PARP (iPARP), dada la estrecha relación que existe entre PARP y progresión del CaP. El empleo de los iPARP en pacientes con CPRC ha mostrado prometedores resultados, sin embargo, la mayoría de los pacientes tienen una respuesta transitoria ya que desarrollan mecanismos de resistencia a la terapia, así como efectos adversos asociados al tratamiento. Por ello, en esta propuesta se desarrollarán terapias más efectivas empleando nanomedicinas poliméricas.

Current PhD Projects

• Design of Polymer-based combination conjugates for Prostate cancer - Sonia Vicente Ruiz (FPI grant) (Co-supervised with Dr. Armiñán)
• Design of Polypeptide-based self-assembled therapeutics for Personalised Medicine in Breast cancer - Oleksandr Zagorodko (Co-supervised with Dr. Nebot)
• Design of polypeptide-based drug delivery systems for topical administration - Irene Dolz Pérez (Co-supervised with Dr. Nebot)
• Identificación De Biotipos Moleculares De Cáncer De Próstata - María García Flores (Co-supervised with Drs. JA López-Guerrero and J Rubio)
• Design of novel targeted Polymer Therapeutics as combination therapy for the treatment of Brain Metastasis – Overcoming the Blood Brain Barrier - Fernanda Rodríguez Otormín (AECC Grant) (Co-supervised with Dr. Duro-Castaño)
• Polypeptidic carriers for the topical delivery of actives and therapeutics -- Daniel Morelló Bolumar, Polypeptide Therapeutic Solutions SL / CIPF (Co-supervised with Dr. Nebot)
• Brain drug delivery using polymer therapeutics as intranasal platform towards pediatric glioma treatment - Tetiana Melnik (AECC Grant) (Co-supervised with Dr. Conejos-Sanchez)
• Development and Optimization of Clinically Relevant Breast Cancer Models for Assessment of Polymer Therapeutics Efficacy - Paz Boix Montesinos (co-supervised with Dr. Armiñán)
• Identification of New Biomarkers and the Development of Polymer-based Combination Conjugates in Metastatic Prostate Cancer - Antoni Serrano Martí (Co-supervised with Dr. Armiñán)
• Development of Analytical Techniques for the Characterization of Polymer Drug Conjugates in Biological Fluids - Snežana Đorđević
• Inflammatory Tumor Microenvironment as Target in the Design of Nanoconjugates for the Treatment of Advanced Breast Cancer (InflaNanoTarget) - Paula Soriano Teruel (Supervised with Mar Orzáez)

Current Masters Projects

• Study of the Role of GTPase Rab11a in Prostate Cancer - Gloria Asensio Juárez
• In vitro and Ex vivo comparative study of antioxidant activity of vitamin E-based treatments - Rocío García Serra
• Estudio del papel de la GTPasa RAb11a en cáncer de próstata - Bruno Domínguez García
• Metabolomic study of an Antibody Drug conjugate for the treatment of CRPC - Jose Vicente Roig Genovés