MULTIFUNCTIONAL NANOQUIMERS BASED ON PROTEINS SUCH AS TERANOSTIC NANOVEICULES FOR MYOCARDIAL INFARCTION THERAPY. (Q3135041): Difference between revisions
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NANOQUIMERS MULTIFONCTIONNELS À BASE DE PROTÉINES TELLES QUE LES NANOVEICULES TERANOSTIC POUR LE TRAITEMENT PAR INFARCTUS DU MYOCARDE. | |||
Revision as of 09:09, 2 December 2021
Project Q3135041 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | MULTIFUNCTIONAL NANOQUIMERS BASED ON PROTEINS SUCH AS TERANOSTIC NANOVEICULES FOR MYOCARDIAL INFARCTION THERAPY. |
Project Q3135041 in Spain |
Statements
102,245.0 Euro
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204,490.0 Euro
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50.0 percent
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16 October 2015
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13 March 2018
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FUNDACION CENTRO NAL DE INV. CARDIOVASCULARES CARLOS III
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40°25'0.12"N, 3°42'12.89"W
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28079
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SALUD, CAMBIO DEMOGRAFICO Y BIENESTAR DE LA SOCIEDAD SON UN RETO QUE AFECTA A TODA LA POBLACION MUNDIAL Y ES UNA REALIDAD BIEN ESTABLECIDA EL TREMENDO IMPACTO QUE EL DESARROLLO DE LA NANOTECNOLOGIA HA TENIDO EN LA SOCIEDAD Y EN ESPECIAL EN LA MEDICINA. SIN EMBARGO, ESTOS NANO-OBJETOS NO SUELEN ESTAR PLENAMENTE CARACTERIZADOS EN EL ENTORNO BIOLOGICO DE APLICACION Y SOLO RECIENTEMENTE LA COMUNIDAD CIENTIFICA HA EMPEZADO A ENFRENTARSE ACTIVAMENTE A ESTA CUESTION. EN CONSECUENCIA, A PESAR DE LAS GRANDES EXPECTATIVAS, LA APLICACION EFICAZ DE LOS NANOMATERIALES EN LA PRACTICA CLINICA SE VE OBSTACULIZADA POR LA LIMITADA COMPRENSION Y CONTROL SOBRE SUS INTERACCIONES CON LOS SISTEMAS COMPLEJOS BIOLOGICOS O PATOLOGICOS. DE HECHO, CUANDO UN NANOMATERIAL (MNPS) ENTRA EN UN ENTORNO FISIOLOGICO, INTERACTUA FUERTEMENTE CON MOLECULAS BIOLOGICAS ENDOGENAS Y SU SUPERFICIE SE RECUBRE INMEDIATAMENTE POR UNA CAPA DE PROTEINAS QUE FORMAN LO QUE SE CONOCE COMO 'CORONA PROTEICA¿ (PC). POR LO TANTO, TODAS LAS FUNCIONALIDADES TERANOSTICA INSERTADAS QUIMICAMENTE EN LA SUPERFICIE DEL NANOVECTOR DURANTE SU SINTESIS SERAN ENVUELTAS Y ENMASCARADAS INFLUYENDO NEGATIVAMENTE SOBRE LA RESPUESTA FISIOLOGICA. EN LOS ULTIMOS DOS DECENIOS, EL INFARTO DE MIOCARDIO (AMI) SE HA CONVERTIDO EN UN PROBLEMA DE SALUD MUNDIAL. ENTRE LAS ESTRATEGIAS TERAPEUTICAS MAS RELEVANTES UTILIZADAS EN ESTA PATOLOGIA, LA ADMINISTRACION DE FACTORES DE CRECIMIENTOS ANGIOGENICOS HA DEMOSTRADO SER ALTAMENTE EFECTIVA. DEBIDO A LA INSURGENCIA DE GRAVES EFECTOS SECUNDARIOS RELACIONADOS CON LA ADMINISTRACION SISTEMICA, EL SUMINISTRO DIRIGIDO DE UNA ADECUADA DOSIS TERAPEUTICA DEL FACTOR DE CRECIMIENTO HA SIDO DESCRITO COMO LA UNICA ALTERNATIVA VIABLE. BASANDOSE EN LOS RETOS ANTERIORMENTE MENCIONADO Y EN BASE A LA FRASE COMUN "SI NO PUEDES VENCERLOS, UNETE A ELLOS", SE PROPONE AQUI UN ENFOQUE SIN PRECEDENTES BASADO EN LA EMULACION DEL MECANISMO DE FORMACION DE PC BIOLOGICA PERO REALIZANDO LA CREACION, DE MANERA CONTROLADA, DE UNA PROTEINA-CORONA ARTIFICIAL (ARTPC) QUE ENVUELVA EL NANOMATERIAL MAGNETICO SELECCIONADO. ESTA CAPA DE PROTEINA ARTIFICIAL (CON LIPASA COMO PLATAFORMA GENERAL MULTIVALENTE PARA LA INCORPORACION EFICIENTE 'A LA CARTA' DE DIFERENTES MOLECULAS) ESTARA COMPUESTA POR QUIMERAS BASADAS EN PROTEINAS MULTIFUNCIONALIDADAS (PX) QUE LLEVAN EN SU SUPERFICIE TODAS LAS FUNCIONALIDADES REQUERIDAS POR LA ACTIVIDAD TERANOSTICA FINAL Y OTORGANDOLE LA DESEADA CAPACIDAD DE EVITAR LA FORMACION DE PC (MNP-PXS). POR LO TANTO UNA BIBLIOTECA DE MNP-PXS TERANOSTICAS SERA PRODUCIDA Y CARACTERIZADA AMPLIAMENTE IN VITRO APLICANDO UN PROTOCOLO ALTAMENTE INTEGRADO (POR EJEMPLO, FISICA, TOXICOLOGICO, PROTEOMICA Y TECNICAS DE CRIBADO DE ALTO CONTENIDO). EL MEJOR CANDIDATO SERA LUEGO UTILIZADO PARA LA EVALUACION IN VIVO DE LA PLANIFICADA ACTIVIDAD TERANOSTICA (MEJORA DE IMAGEN MULTIMODAL + EVALUACION EFECTO TERAPEUTICO) EN EL TRATAMIENTO DEL IMA EN MODELOS ANIMALES. GRACIAS A UN ANALISIS BIOINFORMATICA DE LA GRAN BASE DE DATOS GENERADA CON RESPECTO A LA RELACION DIRECTA ENTRE LA ADSORCION DE PROTEINAS (FORMACION DE PC) Y LAS CARACTERISTICAS MNP-PXS, SE ESPERA PODER DEFINIR EL ASPECTO MECANICISTA DE LA FORMACION DE LA PC EN LA SUPERFICIE DEL NANOMATERIAL. GRACIAS A LA ESTANDARIZACION DE ESTA ESTRATEGIA, SE ESPERA QUE ESTE PROYECTO PUEDA CONVERTIRSE EN UN PARADIGMA DE REFERENCIA PARA EL DISEÑO RACIONAL DE LOS NANOMATERIALES CON POSIBLES APLICACION EN BIOMEDICINA U OTRAS AREAS DE INVESTIGACION A TAMAÑO NANOESCALA. (Spanish)
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HEALTH, DEMOGRAPHIC CHANGE AND WELL-BEING OF SOCIETY ARE A CHALLENGE THAT AFFECTS THE ENTIRE WORLD POPULATION AND IT IS A WELL-ESTABLISHED REALITY THE TREMENDOUS IMPACT THAT THE DEVELOPMENT OF NANOTECHNOLOGY HAS HAD ON SOCIETY AND ESPECIALLY IN MEDICINE. HOWEVER, THESE NANO-OBJECTS ARE OFTEN NOT FULLY CHARACTERISED IN THE BIOLOGICAL ENVIRONMENT OF APPLICATION AND ONLY RECENTLY HAS THE SCIENTIFIC COMMUNITY ACTIVELY BEGUN TO DEAL WITH THIS QUESTION. CONSEQUENTLY, DESPITE HIGH EXPECTATIONS, THE EFFECTIVE APPLICATION OF NANOMATERIALS IN CLINICAL PRACTICE IS HAMPERED BY LIMITED UNDERSTANDING AND CONTROL OVER THEIR INTERACTIONS WITH COMPLEX BIOLOGICAL OR PATHOLOGICAL SYSTEMS. IN FACT, WHEN A NANOMATERIAL (MNPS) ENTERS A PHYSIOLOGICAL ENVIRONMENT, IT STRONGLY INTERACTS WITH ENDOGENOUS BIOLOGICAL MOLECULES AND ITS SURFACE IS IMMEDIATELY COATED BY A LAYER OF PROTEINS THAT FORM WHAT IS KNOWN AS ‘PROTEIN CROWN’ (PC). THEREFORE, ALL TERANOSTIC FUNCTIONALITIES CHEMICALLY INSERTED INTO THE SURFACE OF THE NANOVECTOR DURING ITS SYNTHESIS WILL BE WRAPPED AND MASKED, NEGATIVELY INFLUENCING THE PHYSIOLOGICAL RESPONSE. IN THE LAST TWO DECADES, MYOCARDIAL INFARCTION (AMI) HAS BECOME A GLOBAL HEALTH PROBLEM. AMONG THE MOST RELEVANT THERAPEUTIC STRATEGIES USED IN THIS PATHOLOGY, THE ADMINISTRATION OF GROWTH FACTORS ANGIOGENICOS HAS PROVEN TO BE HIGHLY EFFECTIVE. DUE TO THE INSURGENCY OF SEVERE SIDE EFFECTS RELATED TO SYSTEMIC ADMINISTRATION, THE TARGETED SUPPLY OF AN APPROPRIATE THERAPEUTIC DOSE OF THE GROWTH FACTOR HAS BEEN DESCRIBED AS THE ONLY VIABLE ALTERNATIVE. BASED ON THE CHALLENGES MENTIONED ABOVE AND BASED ON THE COMMON PHRASE “IF YOU CAN'T BEAT THEM, JOIN THEM,” WE PROPOSE HERE AN UNPRECEDENTED APPROACH BASED ON THE EMULATION OF THE MECHANISM OF FORMATION OF BIOLOGICAL PC BUT PERFORMING THE CREATION, IN A CONTROLLED WAY, OF AN ARTIFICIAL PROTEIN-CROWN (ARTPC) THAT WRAPS THE SELECTED MAGNETIC NANOMATERIAL. THIS LAYER OF ARTIFICIAL PROTEIN (WITH LIPASE AS A GENERAL MULTIVALENT PLATFORM FOR THE EFFICIENT INCORPORATION ‘A LA CARTE’ OF DIFFERENT MOLECULES) WILL BE COMPOSED OF CHIMERAS BASED ON MULTIFUNCIONALITY PROTEINS (PX) THAT CARRY ON ITS SURFACE ALL THE FUNCTIONALITIES REQUIRED BY THE FINAL TERANOSTIC ACTIVITY AND GIVING IT THE DESIRED ABILITY TO AVOID PC FORMATION (MNP-PXS). THEREFORE, A LIBRARY OF MNP-PXS TERANOSTICAS WILL BE PRODUCED AND CHARACTERISED EXTENSIVELY IN VITRO BY APPLYING A HIGHLY INTEGRATED PROTOCOL (E.G. PHYSICAL, TOXICOLOGICAL, PROTEOMIC AND HIGH-CONTENT SCREENING TECHNIQUES). THE BEST CANDIDATE WILL THEN BE USED FOR IN VIVO EVALUATION OF PLANNED TERANOSTICA ACTIVITY (IMPROVEMENT OF MULTIMODAL IMAGE + THERAPEUTIC EFFECT EVALUATION) IN THE TREATMENT OF AMI IN ANIMAL MODELS. THANKS TO A BIOINFORMATIC ANALYSIS OF THE LARGE DATABASE GENERATED WITH RESPECT TO THE DIRECT RELATIONSHIP BETWEEN PROTEIN ADSORPTION (PC FORMATION) AND MNP-PXS CHARACTERISTICS, IT IS EXPECTED TO BE ABLE TO DEFINE THE MECHANISTIC ASPECT OF PC FORMATION ON THE SURFACE OF THE NANOMATERIAL. THANKS TO THE STANDARDISATION OF THIS STRATEGY, IT IS EXPECTED THAT THIS PROJECT CAN BECOME A PARADIGM OF REFERENCE FOR THE RATIONAL DESIGN OF NANOMATERIALS WITH POSSIBLE APPLICATION IN BIOMEDICINE OR OTHER AREAS OF RESEARCH AT NANOSCALE SIZE. (English)
12 October 2021
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Madrid
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Identifiers
SAF2014-59118-JIN
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