Development of nanosystems for active tumor targeting in photodynamic therapy

Cancer is one of the major public health problems worldwide. According to the International Agency for Research on Cancer, an estimated 19.3 million new cancer cases and almost 10 million cancer deaths occurred in 2020 [1]. Furthermore, the diagnosis and treatment of cancer have been hampered by the coronavirus disease 2019 (COVID-19) pandemic and it is expected to result in an increased cancer mortality over the next years due to a delay in the diagnoses, and also due to an interruption in the treatments that had been applied to cancer patients. For example, the U.S. National Cancer Institute estimated a 1% increase in deaths related to breast and colorectal cancer over the next 10 years, the equivalent of approximately 10,000 more deaths, due to the impact of the pandemic [2]. This highlights the need to continue in the search of new therapeutic compounds in order to reduce the chance of cancer recurrence after traditional treatments such as surgery and radiotherapy.Some of these new treatments could be used as primary or adjuvant therapeutic options, for instance, photodynamic therapy (PDT) arises as an improved treatment tool due to its highly effective, non-invasive and localized therapeutic action. Taking consideration of the selective action in the irradiation tumor area with PDT, and that it is a treatment that does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, this photo-assisted therapy is positioned as a main and/or adjuvant treatment in the fight against cancer. PDT has been approved by the Food Drug Administration (FDA), and also by other regulatory agencies around the world, to treat a variety of tumors and malignancies in the clinic [3]. For the success of PDT, three elements must converge in tumor cells: photosensitizer (PS) accumulation, light irradiation penetration and the presence of molecular oxygen. More of the recent developments regarding PDT have been made around the generation of new PSs.Fil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentin

Light-activated green drugs: How we can use them in photodynamic therapy and mass-produce them with biotechnological tools

Photodynamic therapy (PDT) is a promising therapeutic approach to manage the resolution of cancer. Plants in nature are one of the potential sources for obtaining new photosensitizers (PSs) that are less toxic than synthetic compounds. Although several works have been done regarding PDT in the last decades, relatively minor attention has been paid to the study of extracts of medicinal plants called photoactivatable "green drugs''. The objective of the review was to identify common photoactive groups of PSs found in nature, mainly obtained from plants, analyzing their photochemical characteristics, and making a detailed botanical description of the plant groups from which they are obtained. In addition, biotechnological strategies in the cultivation of plant-based in vitro systems to produce natural PSs on a large scale are discussed. To accomplish it, the retrieval of potentially relevant studies was done by systematically searching scientific databases like Google Scholar and PubMed between the months of June–December of the year 2020. The main keywords used as search terms were related to plant-based photosensitizers, naturally occurring photosensitizers, phototoxins, plant cell cultures, hairy root cultures. Plant-based photoactivable compounds with an adequate botanical description of known and unknown plants used in PDT for the eradication of tumor cells are mandatory in the field of phytomedicine against cancer. On the other hand, potential PSs could be explored based on phototoxic plant species that were associated with photosensitization in animals and humans over time. The underlying principles of biotechnological processes for obtaining the secondary metabolites were addressed due to the need for new technologies to produce these potential pharmaceuticals drugs in an ecofriendly approach. The successes of plant-based PSs in PDT encourage researchers to work together with botanists to identify natural photoactive compounds from different plant species that remain to be identified or studied, and thus, they use them as alternatives for the synthesis of PSs with minimal side effects, low toxicity and greater selectivity in the different cancer treatments using PDT. Furthermore, novel biotechnology-based breeding techniques such as targeted genome editing methods will provide significant opportunities to produce natural products in plants, mainly when associated with the recent developments in scale-up capability and bioreactor design.Fil: Foresto, Emiliano. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Gilardi, Pamela. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Ibarra, Luis Exequiel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Cogno, Ingrid Sol. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentin

Amplified singlet oxygen generation in metallated-porphyrin doped conjugated polymer nanoparticles

We report on the mechanism and efficiencies of singlet oxygen O2(1Δg) generation of nanoparticles (NP) of the conjugated polymer (CP) poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT) doped with platinum octaethylporphyrin (PtOEP) suspended in water. A detailed study of the photophysics of these NP, using stationary and time-resolved absorption and emission techniques, indicates that O2(1Δg) is generated by the triplet excited state of F8BT and not by that of PtOEP, as previously observed for other porphyrin doped CP NP. O2(1Δg) quantum yields (ΦΔ) were measured by quantifying the characteristic phosphorescence of O2(1Δg) in the NIR region (∼1268 nm). It was found that incorporation of relatively small amounts of PtOEP to F8BT NP results in a significant increase of ΦΔ. NP containing 10% PtOEP (w/w) show a ΦΔ ∼ 0.24, which is 3 times larger than that observed for undoped F8BT NP, and larger than the reported for most water-soluble porphyrins. ΦΔ were also calculated from the oxidation rates (v0) of 3-[10-(2-carboxyethyl)anthracen-9-yl]propanoic acid (ADPA), a well-known chemical O2(1Δg) trap. Unexpectedly, this method was found to significantly overestimate the ΦΔ values due to the adsorption of ADPA on the surface of NP. The ADPA/NP adsorption process was characterized using a simple adsorption model yielding an (average) equilibrium constant of ∼8 × 103 M−1 and an (average) number of NP-binding sites of ∼14000. These results necessarily caution about the use of ADPA as a probe to evaluate ΦΔ in these NP systems. In addition, the interaction of F8BT NP with other anionic, cationic and zwitterionic dyes (dissolved in water) was studied. It was found that even at nano-molar concentrations all the dyes efficiently adsorb on the NP surface. This general and simple self-assembly strategy can be used to prepare superficially-dye-doped CP NP with potentially interesting technological applications.Fil: Spada, Ramiro Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Macor, Lorena Paola. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hernández, Laura. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ponzio, Rodrigo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Ibarra, Luis Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Lorente, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Chesta, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Palacios, Rodrigo Emiliano. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Drogas verdes y Terapia fotodinámica: Una alianza prometedora en la lucha contra el cáncer

La terapia fotodinámica (TFD) es un enfoque terapéutico prometedor en la lucha contra el cáncer. Esta terapia utiliza drogas fotosensibilizadoras, luz y oxígeno para generar especies reactivas del oxígeno(ROS), las cuales son extremadamente tóxicas para las células tumorales. El uso de plantas representa una alternativa alentadora para poder obtener nuevos compuestos terapéuticos denominados "fármacos verdes" que en la TFD son llamados fotoactivables ya que es necesario que se activen en presencia de luz para generar las ROS y producir la muerte de las células tumorales, y por lo tanto esta representa una delas principales ventajas debido a la menor toxicidad en comparación con compuestos sintéticos que son de uso habitual. La búsqueda de nuevos y prometedores fotosensibilizadores obtenidos de plantas para su aplicación en la TFD animan a los investigadores atrabajar junto con botánicos quienes podrán identificar de mejor manera las plantas y sus familias que puedan contener estos compuestos fotoactivos. Además, las nuevas técnicas de reproducción basadas en biotecnología, como los métodos específicos de edición del genoma, brindarán oportunidades importantes para producir productos naturales en plantas,principalmente cuando se asocian con los recientes avances en la capacidad de ampliación y el diseño de biorreactores.Fil: Foresto, Emiliano. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Placci Arditi, Marina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Cogno, Ingrid Sol. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentin

El banco de semillas del suelo. Una metodología experimental sencilla, reproducible y de bajo costo para aprender sobre la biología de las malezas

A pesar de la importancia que presentan las salidas al campo y el trabajo experimental en la sanidad vegetal, las carreras de Ingeniería Agronómica y similares carecen de estas actividades en sus programas. Para abordar esa deficiencia desarrollamos una propuesta basada en una clase experimental usando los bancos de semillas del suelo (BSS) para promover el estudio de la biología y ecología de las malezas en un curso de grado para aspirantes a Ingenieros Agrónomos. Durante el desarrollo de la propuesta, el alumnado realiza recolección de muestras del BSS en un campo agrícola-ganadero sometido a diferentes tipos de labranza y por medio de una metodología que combina salidas al campo, trabajo en laboratorio y procesamiento estadísticos de resultados, evaluando diferentes aspectos del BSS del área de estudio con la entrega de un informe final de la experiencia. La propuesta utiliza materiales de bajo costo y equipamiento que resulta de uso común en cualquier laboratorio universitario, la metodología es sencilla y fácilmente reproducible, como así también, libre de riesgos para la salud humana, siendo fácilmente aplicable en cualquier centro de enseñanza universitario o secundario. Este conjunto de experimentos debería ayudar al alumnado a desarrollar diferentes habilidades como el manejo y diseño de ensayos experimentales y a promover sus capacidades de discutir y resolver problemas prácticos, así como de sacar conclusiones de sus observaciones y los resultados obtenidos. Finalmente, esta actividad práctica les pone en contacto con su futura carrera profesional y, además, les brinda una posibilidad de iniciarse en el campo de la investigación. Esta propuesta tiene como objetivo aumentar la capacidad del alumnado para resolver problemas utilizando métodos científicos flexibles, desarrollar habilidades como el manejo de ensayos experimentales y la capacidad de discutir sus observaciones o resultados obtenidos. Palabras clave: banco de semilla del suelo; malezas; didáctica de las ciencias agronómicas; metodología experimental; educación superior. The soil seed bank: A simple, reproducible and inexpensive experimental methodology to learn about the biology of weeds. Abstract: Despite the importance of field trips and experimental works in plant health, Agronomic Engineering and similar careers lack these types of activities in their programs. To address this deficiency, we developed a proposal based on an experimental class using soil seed banks (SSB) to promote the study of the biology and ecology of weeds in an undergraduate course for aspiring agronomists. During the development of the proposal, the students collect samples from the SSB in an agricultural-livestock field subjected to different types of tillage and through a methodology that combines field trips, laboratory work and statistical processing of results, evaluating different aspects of the SSB of the study area with the delivery of a final report of the experience. The proposal uses low-cost materials and equipment that are commonly present in any university laboratory, the methodology is simple and easily reproducible, as well as free of risks to human health, being applicable in any university or secondary school. This set of experiments should help students to develop different skills such as the management and design of experimental trials, to promote their ability to discuss and solve practical problems, as well as to draw conclusions from their observations and the results obtained. Finally, this practical activity puts them in contact with their future professional career and also gives them a chance to start in the field of research. This proposal aims to increase the ability of students to solve problems using flexible scientific methods and develop skills such as handling experimental trials and discussing their observations or results obtained. Keywords: soil seed bank; weeds; didactics of agricultural sciences; experimental methodology; university educationA pesar de la importancia que presentan las salidas al campo y el trabajo experimental en la sanidad vegetal, las carreras de Ingeniería Agronómica y similares carecen de estas actividades en sus programas. Para abordar esa deficiencia desarrollamos una propuesta basada en una clase experimental usando los bancos de semillas del suelo (BSS) para promover el estudio de la biología y ecología de las malezas en un curso de grado para aspirantes a Ingenieros Agrónomos. Durante el desarrollo de la propuesta, el alumnado realiza recolección de muestras del BSS en un campo agrícola-ganadero sometido a diferentes tipos de labranza y por medio de una metodología que combina salidas al campo, trabajo en laboratorio y procesamiento estadísticos de resultados, evaluando diferentes aspectos del BSS del área de estudio con la entrega de un informe final de la experiencia. La propuesta utiliza materiales de bajo costo y equipamiento que resulta de uso común en cualquier laboratorio universitario, la metodología es sencilla y fácilmente reproducible, como así también, libre de riesgos para la salud humana, siendo fácilmente aplicable en cualquier centro de enseñanza universitario o secundario. Este conjunto de experimentos debería ayudar al alumnado a desarrollar diferentes habilidades como el manejo y diseño de ensayos experimentales y a promover sus capacidades de discutir y resolver problemas prácticos, así como de sacar conclusiones de sus observaciones y los resultados obtenidos. Finalmente, esta actividad práctica les pone en contacto con su futura carrera profesional y, además, les brinda una posibilidad de iniciarse en el campo de la investigación. Esta propuesta tiene como objetivo aumentar la capacidad del alumnado para resolver problemas utilizando métodos científicos flexibles, desarrollar habilidades como el manejo de ensayos experimentales y la capacidad de discutir sus observaciones o resultados obtenidos. Palabras clave: banco de semilla del suelo; malezas; didáctica de las ciencias agronómicas; metodología experimental; educación superior. The soil seed bank: A simple, reproducible and inexpensive experimental methodology to learn about the biology of weeds. Abstract: Despite the importance of field trips and experimental works in plant health, Agronomic Engineering and similar careers lack these types of activities in their programs. To address this deficiency, we developed a proposal based on an experimental class using soil seed banks (SSB) to promote the study of the biology and ecology of weeds in an undergraduate course for aspiring agronomists. During the development of the proposal, the students collect samples from the SSB in an agricultural-livestock field subjected to different types of tillage and through a methodology that combines field trips, laboratory work and statistical processing of results, evaluating different aspects of the SSB of the study area with the delivery of a final report of the experience. The proposal uses low-cost materials and equipment that are commonly present in any university laboratory, the methodology is simple and easily reproducible, as well as free of risks to human health, being applicable in any university or secondary school. This set of experiments should help students to develop different skills such as the management and design of experimental trials, to promote their ability to discuss and solve practical problems, as well as to draw conclusions from their observations and the results obtained. Finally, this practical activity puts them in contact with their future professional career and also gives them a chance to start in the field of research. This proposal aims to increase the ability of students to solve problems using flexible scientific methods and develop skills such as handling experimental trials and discussing their observations or results obtained. Keywords: soil seed bank; weeds; didactics of agricultural sciences; experimental methodology; university educatio

Polyaniline nanofibers: Acute toxicity and teratogenic effect on Rhinella arenarum embryos

The fate and effect of nanomaterials in the environment is of paramount importance towards the technological application of the materials. This work shows the ecotoxicological potential of polyaniline (PANI) nanofibers in the larvae Rhinella arenarum by means of AMPHITOX test. Acute toxicity of PANI nanofibers towards embryos of the common South American toad R. arenarum (Anura: bufonidae) was evaluated in the premetamorphosis (stage 25) larvae. The exposure of R. arenarum larvae to at dose of 150, 250 and 400mgL-1 resulted in 100% viability within 96h exposure. The embryos at 2-4 blastomers stage (early life stage teratogenic test) revealed that embryos were not killed and no teratogenic effects were observed when embryos were incubated with PANI nanofibers (150 and 250mgL-1), while only a growth retardation of embryos was induced at levels of 250mg PANI nanofibersL-1. On the other hand, at 400mgL-1 concentration, a reduction in the body length of larvae and tail malformation was observed. This results suggest that a concentration-dependent toxicity is operative, typified by phenotypes that had abnormal body axes. The presence of PANI nanofibers in gut contents and its excretion by larval stages of R. arenarum was confirmed by UV-visible spectroscopy.Fil: Yslas, Edith Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Ibarra, Luis Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Peralta, Damian Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Barbero, César Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Rivarola, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Bertuzzi, Mabel Lucia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentin

Optimization of Short RNA Aptamers for TNBC Cell Targeting

Triple-negative breast cancer (TNBC) is an aggressive cancer with limited targeted therapies. RNA aptamers, suitably chemically modified, work for therapeutic purposes in the same way as antibodies. We recently generated 2′ Fluoro-pyrimidines RNA-aptamers that act as effective recognition elements for functional surface signatures of TNBC cells. Here, we optimized three of them by shortening and proved the truncated aptamers as optimal candidates to enable active targeting to TNBC. By using prediction of secondary structure to guide truncation, we identified structural regions that account for the binding motifs of the full-length aptamers. Their chemical synthesis led to short aptamers with superb nuclease resistance, which specifically bind to TNBC target cells and rapidly internalize into acidic compartments. They interfere with the growth of TNBC cells as mammospheres, thus confirming their potential as anti-tumor agents. We propose sTN145, sTN58 and sTN29 aptamers as valuable tools for selective TNBC targeting and promising candidates for effective treatments, including therapeutic agents and targeted delivery nanovectors.Fil: Camorani, Simona. Institute Of Experimental Endocrinology And Oncology; ItaliaFil: D'Argenio, Annachiara. Institute Of Experimental Endocrinology And Oncology; ItaliaFil: Agnello, Lisa. Institute Of Experimental Endocrinology And Oncology; ItaliaFil: Nilo, Roberto. Institute Of Experimental Endocrinology And Oncology; ItaliaFil: Zanetti, Antonella. Institute Of Biostructures And Bioimaging; ItaliaFil: Ibarra, Luis Exequiel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentina. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Fedele, Monica. Institute Of Experimental Endocrinology And Oncology; ItaliaFil: Cerchia, Laura. Institute Of Experimental Endocrinology And Oncology; Itali

Iron oxide incorporated conjugated polymer nanoparticles for simultaneous use in magnetic resonance and fluorescent imaging of brain tumors

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplat-forms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functional-ization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe3 O4 and NiFe2 O4 nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T2 WI) signals and T2 values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.Fil: Arias Ramos, Nuria. Consejo Superior de Investigaciones Científicas; EspañaFil: Ibarra, Luis Exequiel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Serrano Torres, María. Consejo Superior de Investigaciones Científicas; EspañaFil: Yagüe, Balbino. Consejo Superior de Investigaciones Científicas; EspañaFil: Caverzan, Matias Daniel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; ArgentinaFil: Chesta, Carlos Alberto. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: Palacios, Rodrigo Emiliano. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Química; ArgentinaFil: López Larrubia, Pilar. Consejo Superior de Investigaciones Científicas; Españ

Development and biological evaluation of pNIPAM-based nanogels as vaccine carriers

“Smart” nanogels are an attractive tool for the development of new strategies of immunization in veterinary medicine. Here, we reported the synthesis and physicochemical characterization of thermoresponsive nanogels based on poly(N-isopropylacrylamide) (pNIPAM) and their in vitro, ex vivo and in vivo (mice model) performance. Smart nanogels of ca. 250 nm, with a transition temperature of 32 °C were obtained by precipitation polymerization. Assays to evaluate pNIPAM nanogels cytotoxicity were performed in different cell lines showing high biocompatibility (>70 %). The efficient internalization of the system was studied by confocal microscopy as well as flow cytometry. The ability to protect and deliver antigens was analyzed using the outer membrane lipoprotein A (OmlA), an important virulence factor of Actinobacillus pleuropneumoniae (App) cause of porcine pleuropneumonia. This lipoprotein was synthesized by recombinant technology and its technique was also described. The biodistribution of pNIPAM nanogels administered intranasally was performed in vivo and ex vivo through Pearl Imaging System, which showed that nanogels were kept mostly in the lungs during the evaluated time. Besides, the efficacy of the proposal nanogel-based vaccine was studied in vivo by measuring the antibody titers of BALB/c mice inoculated with OmlA encapsulated into pNIPAM nanogels compared to OmlA plus aluminum hydroxide adjuvant. The results proved the ability of nanogels to stimulate a humoral immune response. Therefore, we have demonstrated that pNIPAM nanogels can be used as an efficient platform for vaccine nanocarriers.Fil: Soriano Pérez, María Laura. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Funes, Javier Alejandro. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Flores Bracamonte, María Carolina. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Instituto de Ciencias Veterinarias. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Ciencias Veterinarias.; ArgentinaFil: Ibarra, Luis Exequiel. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Forrellad, Marina Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cariddi, Laura Noelia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Biotecnología Ambiental y Salud - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Salinas, Facundo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Alustiza, Fabrisio Eduardo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Córdoba. Estación Experimental Agropecuaria Marcos Juárez; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Molina, María Alejandra. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentin

Cellular Trojan horses for delivery of nanomedicines to brain tumors: Where do we stand and what is next?

Brain tumors have the ability to exist even at a small size, thus making them extremely difficult to diagnose and cure. For this reason they are often considered as one of the most highly destructive and lethal groups of brain diseases, being responsible for the fourth-highest number of years of life lost in the world?s population [1]. The incidence of this type of cancer is increasing; also, mortality rate has been reported to be 4.6 per 100,000 person-years worldwide [2]. These tumors seem to be more and more frequent, not only because of a true increase in their incidence, but also due to the increase in life expectancy of the general population and technological advances that allow an opportune and early diagnosis. Brain cancers, also referred as central nervous system (CNS) cancers, are a group of several types of tumors from different origins, mostly from neuronal and glial precursor cells. The most common histological types of primary CNS tumors are gliomas?a group of malignant brain tumors, including high-grade glioma or glioblastoma (GBM) and low-grade gliomas (astrocytoma, oligodendroglioma). Within these types of gliomas, GBM is still associated with an extremely poor patient prognosis with no curative treatment options available and the 5-year survival of GBM-diagnosed patients remains lower than 6% [3]. Despite a greater understanding of the disease over the last few years, first-line treatment options in the management of GBM remain as tumor resection, radiotherapy and the administration of chemotherapeutic alkylating agents such as temozolomide [4]. Malignant gliomas are a source of mortality and morbidity for which diagnosis and treatment require extensive resource allocation for more sophisticated diagnostic and therapeutic technologies [5]. In this sense, nanomedicine brings novel nano-based drug developments to expand the therapeutic options for the management of brain tumors, specifically for GBM [6,7]. Over the past two decades, many research groups have reported the development of different types of theragnostic nanoparticles for GBM treatment, and other forms of CNS cancers, including magnetic nanoparticles [8], gold nanoparticles [9], liposomes [10], carbon-based nanostructures [11] and polymeric nanoparticles [12]. Although several in vitro and in vivo studies have been performed to demonstrate the efficacy and therapeutic potential of these nanotechnology and nanocarrier-based treatments, only a few of them have completed clinical trials on their own or in combination with other treatments.Ideally, the design of multifunctional nanoparticulate brain tumor-targeted delivery systems involves bioconjugation with ligands, antibodies, aptamers or peptides, which increase accumulation specifically at the tumor site within the CNS and favors minimal toxicity in healthy tissue. However, there are numerous barriers to overcome if this treatment strategy based on active targeting is to be successful. For instance, the common method to achieve intracerebral location is intravascular administration, and once nanoparticles are in the bloodstream, they face several barriers or obstacles until they reach the brain parenchyma. The first of which is the opsonization of plasma proteins and formation of a protein corona around the nanoparticles, which, in turn, favors phagocytosis by the mononuclear phagocytic system (MPS) from liver, spleen and lungs leading to a rapid clearance from the circulation with limited circulation time, and thus to reduced crossing of the blood-brain barrier (BBB). The brain is protected by the highly specialized BBB, which tightly regulates the transport of metabolically important molecules between the blood and the brain and thus, the BBB constitutes another barrier that nanoparticles need to overcome. This barrier is formed by specialized microvessel endothelial cells and pericytes. In addition, astrocytes and interneurons also contribute to the BBB structure. On the other hand, brain tumors, especially malignant gliomas, possess a blood?brain tumor barrier (BBTB) which is formed during tumor progression [13]. A feature of GBM tumor heterogeneity is the coexistence of both types of barriers with differential permeability to drugs in the different tumor regions. Nano-based therapeutics need to be able to overcome these barriers and penetrate the brain to reach the tumor cells. This has led to the search for additional ways to deliver nanomaterials to the CNS by using cell-based delivery systems with the purpose of conquering the traditional active targeting methods by avoiding or overcoming the aforementioned obstacles.Fil: Ibarra, Luis Exequiel. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Departamento de Biología Molecular; Argentin