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Nanopartículas Farmacocinéticas

El grupo de diseño y farmacodinámica de nanopartículas del Vall d’Hebron Instituto de Investigación se centra en la síntesis, caracterización y aplicaciones de nanopartículas inorgánicas en el campo de la medicina. Al controlar el núcleo inorgánico (tamaño, estructura y forma) y la unión de moléculas a su superficie, diseñamos nanopartículas que pueden interactuar con los sistemas biológicos de una manera específica. También ponemos especial énfasis en la seguridad, viabilidad, ampliación, aplicabilidad y otros aspectos del diseño de nanopartículas para medicina. 


Nuestro grupo está dirigido por el Prof. Víctor Puntes, quien tiene una Cátedra de Investigación ICREA. Dado que una gran parte de nuestro trabajo exige una experiencia altamente multidisciplinaria, mantenemos colaboraciones con físicos, biólogos, inmunólogos, oncólogos, y otros, de Europa, China y los EE.UU. El trabajo del grupo ha dado lugar a varias patentes y creación de spin-off como Nanotargeting y Applied Nanoparticles.

Equipo

Joan Comenge Farré

Joan Comenge Farré

Investigador postdoctoral
Nanopartículas Farmacocinéticas
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Ramon Gonzalez Rioja

Ramon Gonzalez Rioja

Investigador predoctoral
Nanopartículas Farmacocinéticas
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Joana Ramis Garcia

Joana Ramis Garcia

Investigador predoctoral
Nanopartículas Farmacocinéticas
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Lena Nerea Montaña Ernst

Lena Nerea Montaña Ernst

Técnico de investigación
Nanopartículas Farmacocinéticas
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Victor Franco Puntes

Victor Franco Puntes

Jefe de grupo
Nanopartículas Farmacocinéticas
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Joan Comenge Farré

Joan Comenge Farré

Investigador postdoctoral
Nanopartículas Farmacocinéticas
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Ramon Gonzalez Rioja

Ramon Gonzalez Rioja

Investigador predoctoral
Nanopartículas Farmacocinéticas
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Joana Ramis Garcia

Joana Ramis Garcia

Investigador predoctoral
Nanopartículas Farmacocinéticas
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Lena Nerea Montaña Ernst

Lena Nerea Montaña Ernst

Técnico de investigación
Nanopartículas Farmacocinéticas
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Victor Franco Puntes

Victor Franco Puntes

Jefe de grupo
Nanopartículas Farmacocinéticas
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Líneas de investigación

Design of nanoparticles for useful applications

Getting advantages from the accumulated experience, I will study the most problematic points related to the growth of multi-component materials and hollow structures. We are preparing complex multifunctional environment responsive NPs comprising different families: i) metallic, ii) metal oxide, iii) semiconductor and iv) oxides of semiconductor. Beyond synthesis, I will focus on the precise characterization of the obtained NPs in terms of their reactivity and physico-chemical properties to precisely correlate morphology with activity. The synthesis of advanced NPs will be carry out, primarily, following seeding-growth approaches or by combining the simultaneous or sequential injection of precursor solutions, surfactant mixtures. The temperature of the solution will be adjusted in order to kinetically control the formation of the NPs and reaction times will be controlled to induce digestion processes and re-crystallizations/controlled sintering when required.  I will use mixtures of surfactants or reducing agents and coordinating complexes under controlled atmospheres, intending to independently modify the solubility of the monomer, the nucleation radii, the growing rate and the morphology of the growing structure (by stabilizing different crystals phases and therefore lowering their energy and accelerating selected competing reactions). Hollow metal structures will be synthesized following a multi-step procedure. In the first step, Ag nanocubes are synthesized by known techniques (such as polyol synthesis). Polymetallic hollow NPs with very different morphology  and composition, will be obtained by the simultaneous or sequential action of galvanic replacement and the Kirkendall effect in order to control the number and morphology of void spaces inside a single NP, and the chemical transformation of NPs such as cation release/exchange. This allows the production of, among other, monodisperse single- and double-walled nanoboxes or noble metal fullerenes, in high yields and scalable synthesis.


a. APPLICATION ON MEDICINE.

Nanotechnology’s ability to shape matter at the scale of molecules is opening the door to a new generation of diagnostics, imaging agents and drugs/therapies for detecting and treating disease. But perhaps more important,  it is allowing to combine a series of advances, creating nanosized particles that may for example contain drugs designed to kill damaged cells together with targeting compounds designed to home-in on malignancies, and imaging agents designed to light up even the earliest stage of disease. For example NPs are perfect candidates to be used in anticancer therapy since they showed passive accumulation in solid tumours due to the Enhanced Permeation and Retention effect (EPR). Is in this context that nanotechnology emerges as a “disruptive technology” with a great potential to contribute to improve treatment by generating new diagnostic and therapeutic products. Its fields of action can be classified in diagnosis, imaging, drug delivery, hyperthermia, theranostics, the simultaneous diagnosis and therapy, and therapy monitoring.


It has been acknowledged that one of the most promising societal impacts of nanotechnology is in the area of nanomedicine. Personalized health care, rational drug design and targeted drug delivery are some of the proposed benefits of a nanomedicine-based approach to therapy. On this subject, my lines of work are: i) Nanooncology, the use of nanoparticles for diagnosis and treatment of cancer. Here I am developing NP-Biomolecule (as AuNP-Antibody) for detection (as lung cancer in breath or circulating cancer cells) and AuNP and Fe3O4 NP for diagnosis/imaging. I continue my work carrying antitumoral drugs with AuNPs (as cisplatin, oxaliplatin, carboplatin, doxorubicin, and sorafenib) and their use as radiotherapy enhancers or hyperthermia agents. ii) Immunology. Significantly important is the interaction of NPs with the immune system. Because one cannot put stuff inside the body without asking the immune system for permission, I am studying the effect of NP on antigen presentation, to then avoid immune detection (for a drug delivery vehicle) or design prophylactic and therapeutic vaccines (for molecular scaffolds). This includes as much AuNPs decorated with antigens as redox active anti-inflammatory CeO2 NPs. iii) Antimicrobial NPs. The emergence of antibiotic resistant strains of common pathogens is a major threat to health and is already putting tremendous pressure on health services worldwide. It has been shown that positive (cationic) nanoparticles show toxic effects to prokaryote, as defensines do. Also, silver, iron or cerium NPs, yield ions that are toxic for prokaryote cells (but well tolerated in eukaryote), acting as disinfectant and bacteriostatic agents. iv) Nanosafety: the prevention of unwanted effects produced by nanoparticles. This is one of our core-expertise areas and I have been working on it, developing NP models for toxicity and ecotoxicity testing, since FP06. My job is to understand which features of NPs poses health threats and then modify the NPs and the way they are used, to avoid the related hazards or exposure (risks) while maintaining the parental desired NP properties.


All this efforts have been translated into the creation of a spin-off company to exploit this knowledge: Nanotargeting (www.nanotargeeting.com), who is actually performing the regulatory preclinical studies and preparing the phase I clinical trials of Aurocis (cisplatin bounded AuNPs).



b. APPLICATION ON ENERGY.

We are facing energy and environmental threats that challenge our world: decrease/consumption of the fossil fuel reserves, global increase in energy demand, increasing pollution and the need to improve the processing of organic waste into a sustainable waste management, since damage to the environment is sooner or later translated into an energy cost. I am working on the design of advanced catalyst (multimetallic and heterodimer NPs) that are able to improve energy-chemical processes. Interestingly, energy harvesting and energy transfer processes are based on physic-chemical principles (electromagnetism) at the scale of few nm, from photosynthesis to electrical transport. I am also working on the design of a new generation of NPs for the production of hydrogen (with CdSe-Pt NPs) for reduction process and transform biomass and produce biofuels. Also I work on the use of iron oxide NPs to boost Biogas production thanks to the fact that iron ions are essential for the bacterial consortia responsible for the degradation and transformation of organic matter into methane. Our approach consists on the use of small concentrations of iron oxide nanoparticles designed and functionalized such that they progressively dispensing active iron ions at the necessary dose (not too low, not too high) for the bacteria, in analogy to sustained drug delivery, boosting methane production up to 300%. This work has been patent and it has received funds from the Bill and Melinda Gates foundation. This project has been granted the second SEGIB international prize and received support from the Programa Emprendedores of the REPSOL foundation leading to the creation of a Spin-Off, Applied Nanoparticles, dedicated to nanotechnology and energy/environment solutions which has, among other, the mission to exploit our Biogas enhanced production patent. I would like to stress that to me energy and environment are closely linked, while indeed, health and environment, are also extremely connected, since the health of the environment determine our morbidity. Regarding environment we address two issues, environmental toxicity of NPs and environmental remediation with NPs. I also focus on the electrochemical oxidation of molecules with our hollow Pt NPs where we are observing also important reactivity (and efficiency) boosts. Finally, I started in collaboration with the chemical engineering department of the UAB, with funding from the Fundación Ramón Areces, the study of nanostructures for the absorption of CO2, in such a way that in the future, the photocatalysis will reduce CO2 to other C species (CO, CH4, CH3OH, CHOOH) and it will be oxydized to recover energy and absorbed to avoid emissions and be transformed into a raw material in a close carbon cycle (note that 75% of south Africa gasoline is synthetic).


My work has position me as a privileged observer of the development of nanotechnology allowing me to advise and communicate to a broad audience. This is translated in participating as Project (e.g.: serenade-labex) or Industry (Nanonica) Scientific Advisor or communicating Science to Society, I am specially proud about the ebook “Nanoparticles before Nanotechnology” with more than 14.000 downloads. Also, the  reporting of my activities in international media, as the BBC or The Guardian also indicates the societal the impact of my work.

IP: Victor Franco Puntes

Proyectos

Next generation serology: Immune profiling via graphene-enhanced DNA scaffold sensors – SerDNA

IP: Victor Franco Puntes
Colaboradores: -
Entidad financiadora: Ministerio de Ciencia e Innovación-MICINN
Financiación: 66250
Referencia: CPP2023-010774
Duración: 01/11/2024 - 31/10/2027

Ministerio de Ciencia

Buscando el camino para la autosuficiencia: preservación corneal con nuevos antioxidantes minerales (nanopartículas de óxido de cerio). Proyecto PRE-CO-CE.

IP: Anna Vilarrodona Serrat
Colaboradores: Alberto Sandiumenge Camps, Joan Comenge Farré, Victor Franco Puntes, Elisabeth Navas Moya
Entidad financiadora: Fundación Invest. Médica Mutua Madrileña
Financiación: 109998
Referencia: FMM24VILARODONA
Duración: 16/09/2024 - 15/09/2027

Nanopartículas de CeO2 para la Regulación Metabólica y el Tratamiento del Estrés Oxidativo y Enfermedades (TRANSCERIA)

IP: Victor Franco Puntes
Colaboradores: Joan Comenge Farré, Lena Nerea Montaña Ernst
Entidad financiadora: Ministerio de Ciencia e Innovación-MICINN
Financiación: 187500
Referencia: PID2023-148967OB-C21
Duración: 01/09/2024 - 31/12/2028

Ministerio de Ciencia

A new formulation of cerium oxide nanoparticles as adjuvant for retinal anti-angiogenesis therapy.

IP: Victor Franco Puntes
Colaboradores: -
Entidad financiadora: Agència Gestió Ajuts Universitaris i de Recerca
Financiación: 150000
Referencia: 2023 PROD 00200
Duración: 01/02/2024 - 31/07/2025

Publicaciones

The development of highly dense highly protected surfactant ionizable lipid RNA loaded nanoparticles.

PMID: 36923400
Revista: Frontiers in Immunology
Año: 2023
Referencia: Front Immunol. 2023 Feb 27;14:1129296. doi: 10.3389/fimmu.2023.1129296. eCollection 2023.
Factor de impacto:
Tipo de publicación: Revisión en revista internacional
Autores: Bastus, Neus G; Gonzalez-Rioja, Ramon; Puntes, Victor; Salazar, Vivian A et al.
DOI: 10.3389/fimmu.2023.1129296

Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration.

PMID: 36979013
Revista: Antioxidants
Año: 2023
Referencia: Antioxidants (Basel). 2023 Mar 21;12(3):765. doi: 10.3390/antiox12030765.
Factor de impacto:
Tipo de publicación: Artículo en revista internacional
Autores: Bastus, Neus G; Casals, Eudald; Casals, Gregori; Ernst, Lena M; Fernandez-Varo, Guillermo; Gusta, Muriel F; Jimenez, Wladimiro; Mondragon, Laura; Puntes, Victor; Ramis, Joana et al.
DOI: 10.3390/antiox12030765

Asymmetrical Plasmon Distribution in Hybrid AuAg Hollow/Solid Coded Nanotubes.

PMID: 36985887
Revista: Nanomaterials
Año: 2023
Referencia: Nanomaterials (Basel). 2023 Mar 9;13(6):992. doi: 10.3390/nano13060992.
Factor de impacto:
Tipo de publicación: Artículo en revista internacional
Autores: Arbiol, Jordi; Arenal, Raul; Bastus, Neus G; Genc, Aziz; Patarroyo, Javier; Puntes, Victor; Sancho-Parramon, Jordi et al.
DOI: 10.3390/nano13060992

Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents.

PMID: 37049267
Revista: Nanomaterials
Año: 2023
Referencia: Nanomaterials (Basel). 2023 Mar 25;13(7):1174. doi: 10.3390/nano13071174.
Factor de impacto:
Tipo de publicación: Artículo en revista internacional
Autores: Bastus, Neus G; Bigini, Paolo; Chakraborty, Indranath; Cui, Daxiang; Masood, Atif; Morelli, Annalisa; Parak, Wolfgang J; Pelaz, Beatriz; Puntes, Victor; Salmona, Mario et al.
DOI: 10.3390/nano13071174

Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro-In Vivo Correlation.

PMID: 35159859
Revista: Nanomaterials
Año: 2022
Referencia: Nanomaterials (Basel). 2022 Feb 1;12(3). pii: nano12030511. doi: 10.3390/nano12030511.
Factor de impacto: 5.076
Tipo de publicación: Artículo en revista internacional
Autores: Manova, Alena; Bastus, Neus G; Moriones, Oscar H; Kohl, Yvonne; Dusinska, Maria; Runden-Pran, Elise; Puntes, Victor; Nelson, Andrew; Gabelova, Alena; Simon, Peter et al.
DOI: 10.3390/nano12030511

How Does Immunomodulatory Nanoceria Work? ROS and Immunometabolism.

PMID: 35401546
Revista: Frontiers in Immunology
Año: 2022
Referencia: Front Immunol. 2022 Mar 17;13:750175. doi: 10.3389/fimmu.2022.750175. eCollection 2022.
Factor de impacto: 7.561
Tipo de publicación: Artículo en revista internacional
Autores: Ernst, Lena M, Puntes, Victor et al.
DOI: 10.3389/fimmu.2022.750175

The Interactions between Nanoparticles and the Innate Immune System from a Nanotechnologist Perspective.

PMID: 34835755
Revista: Nanomaterials
Año: 2021
Referencia: Nanomaterials (Basel). 2021 Nov 6;11(11). pii: nano11112991. doi: 10.3390/nano11112991.
Factor de impacto: 5.076
Tipo de publicación: Revisión en revista internacional
Autores: Ernst, Lena M, Casals, Eudald, Italiani, Paola, Boraschi, Diana, Puntes, Victor et al.
DOI: 10.3390/nano11112991

Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells.

PMID: 34394703
Revista: Nano Today
Año: 2021
Referencia: Nano Today. 2021 Feb;36. doi: 10.1016/j.nantod.2020.101056. Epub 2020 Dec 20.
Factor de impacto: 20.722
Tipo de publicación: Artículo en revista internacional
Autores: Buzon, Maria J, Puntes, Victor, Genesca, Meritxell, Astorga-Gamaza, Antonio, Vitali, Michele, Borrajo, Mireya L, Jaime, Carlos, Bastus, Neus, Serra-Peinado, Carla, Luque-Ballesteros, Laura et al.
DOI: 10.1016/j.nantod.2020.101056

Simple spectroscopic determination of the hard protein corona composition in AuNPs: albumin at 75.

PMID: 32692793
Revista: Nanoscale
Año: 2020
Referencia: Nanoscale. 2020 Aug 7;12(29):15832-15844. doi: 10.1039/d0nr02379e. Epub 2020 Jul 21.
Factor de impacto: 6.895
Tipo de publicación: Artículo en revista internacional
Autores: Vitali, Michele, Casals, Eudald, Canals, Francesc, Colome, Nuria, Puntes, Victor et al.
DOI: 10.1039/d0nr02379e

Tesis

Gold Nanoparticles as Drug Delivery Agents: Detoxifying the Chemotherapeutic Drug Cisplatin

Doctorando: Joan Comenge Farré
Director/es: Victor Franco Puntes
Universidad: Universidad Autònoma de Barcelona
Año: 2013

Actualidad

Noticias

El trabajo busca una nueva estrategia terapéutica más efectiva para tratar las malformaciones arteriovenosas cerebrales, una de las causas principales de ictus en menores y jóvenes.

La Dra. Anna Vilarrodona lidera el estudio que pretende aumentar el tiempo de conservación de las córneas donadas para trasplante.

Profesionales sanitarios y de investigación se han reunido para unir sinergias y buscar soluciones innovadoras.