Arana-Alonso, S. (Sergio)
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- Glass-coated ferromagnetic microwire-induced magnetic hyperthermia for in vitro cancer cell treatment(Elsevier, 2019) Arana-Alonso, S. (Sergio); Lizarbe-Sancha, S. (Sara); Zhukova, V. (Valentina); Campisi, J. (Jay); Martínez-de-Apellaniz, I. (Ion); Zhukov, A. (Arcady); Mitxelena-Iribarren, O. (Oihane); Mujika-Garmendia, M. (Maite)Limitations in effectiveness and the invasive nature of current cancer treatment options emphasize the need for further clinical advancements. Among other approaches, targeted hyperthermia is as a new strategy aimed at targeting cancerous cells to improve the efficacy of radiotherapy or cytotoxic drugs. However, the testing of magnetic vehicles has mainly focused on the use of nanoparticles. In this work, Fe77B10Si10C3 glass-coated amorphous magnetic microwires were assessed for the first time as magnetic vehicles with high potential for the localized heating of osteosarcoma cells by means of an AC magnetic field. The results from the in vitro assays performed inside a microfluidic device demonstrated the ability of these magnetic microwires to induce malignant cell death. Exposing the system to different magnetic fields for less than 1 h provoked a reduction up to 89% of the osteosarcoma cell population, whereas healthy myoblastoma cells remained nearly unaffected. The proposed technology demonstrates in vitro the effectiveness of these microwires as vehicles for targeted magnetic hyperthermia.
- Evaluation of the degradation of materials by exposure to germicide UV-C light through colorimetry, tensile strength and surface microstructure analyses(Elsevier, 2022) Arana-Alonso, S. (Sergio); Sierra-García, J.E. (Jesús Enrique); Smerdou, C. (Cristian); Lorenzo, E.; Mitxelena-Iribarren, O. (Oihane); Guillen-Grima, F. (Francisco); Rodriguez-Merino, F. (Fernando); Mondragon, B. (Beñat)Due to the COVID19 pandemic, solutions to automate disinfection using UV-C combined with mobile robots are beginning to be explored. It has been proved that the use of these systems highly reduces the risk of contagion. However, its use in real applications is not being as rapid as it needs to be. One of the main market input barriers is the fear of degrading facilities. For this reason, it is crucial to perform a detailed study on the degradation effect of UV-C light on inert materials. This experimental study proves that, considering exposition times equivalent to several work years in hospital rooms, only the appearance of the material is affected, but not their mechanical functionalities. This relevant result could contribute to accelerate the deployment of these beneficial disinfection technologies. For that purpose, a colorimetry test, tensile strength test, and analysis of the surface microstructure were carried out. The results showed that polymers tend to turn yellow, while fabrics lose in- tensity depending on the color. Red is hardly affected by UV-C, but blue and green are. Thus, this study con- tributes to the identification of the best materials and colors to be used in rooms subjected to disinfection processes. In addition, it is shown how the surface microstructure of the materials is altered in most of the materials, but not the tensile strength of the fabrics
- Drug-loaded PCL electrospun nanofibers as anti-pancreatic cancer drug delivery systems(Springer, 2023-07) Arana-Alonso, S. (Sergio); Riera-Pons, M. (Marc); Padillo-Ruiz, J. (Javier); Mitxelena-Iribarren, O. (Oihane); Pereira, S. (Sheila); Calero-Castro, F.J.(Francisco José); Mujika-Garmendia, M. (Maite); Castillo-Tuñon, J.M.(Juan Manuel)Cancer is one of the main causes of death worldwide, being pancreatic cancer the second deadliest cancer in Western countries. Surgery, chemotherapy and radiotherapy form the basis of pancreatic cancer's current treatment. However, these techniques have several disadvantages, such as surgery complications, chemotherapy systemic side effects and cancer recurrence. Drug delivery systems can reduce side effects, increasing the effectivity of the treatment by a controlled release at the targeted tumor cells. In this context, coaxial electrospun fibers can increase the control on the release profile of the drug. The aim of this study was to encapsulate and release different anticancer drugs (5-Fluorouracil and Methotrexate) from a polymeric fiber mat. Different flows and ratios were used to test their effect on fiber morphology, FTIR spectrum, drug encapsulation and release. Good integration of the anticancer drugs was observed and the use of a desiccator for 24 h showed to be a key step to remove solvent remanence. Moreover, the results of this study demonstrated that the polymeric solution could be used to encapsulate and release different drugs to treat cancers. This makes coaxial electrospinning a promising alternative to deliver complex chemotherapies that involve more than one drug, such as FOLFIRINOX, used in pancreatic cancer treatment.
- A versatile cancer cell trapping and 1D migration assay in a microfluidic device(2019-07) Arana-Alonso, S. (Sergio); Olaizola, S.M. (Santiago Miguel); Hansford, D.J.(Derek J.); Hisey, C.L.(Colin L.); Mitxelena-Iribarren, O. (Oihane); Benavente-Babace, A. (Ainara); Mujika-Garmendia, M. (Maite); Martínez-Calderón, M. (Miguel); Gordon, J.B. (Jaymeson B.)Highly migratory cancer cells often lead to metastasis and recurrence and are responsible for the high mortality rates in many cancers despite aggressive treatment. Recently, the migratory behavior of patient-derived glioblastoma multiforme cells on microtracks has shown potential in predicting the likelihood of recurrence, while at the same time, antimetastasis drugs have been developed which require simple yet relevant high-throughput screening systems. However, robust in vitro platforms which can reliably seed single cells and measure their migration while mimicking the physiological tumor microenvironment have not been demonstrated. In this study, we demonstrate a microfluidic device which hydrodynamically seeds single cancer cells onto stamped or femtosecond laser ablated polystyrene microtracks, promoting 1D migratory behavior due to the cells' tendency to follow topographical cues. Using time-lapse microscopy, we found that single U87 glioblastoma multiforme cells migrated more slowly on laser ablated microtracks compared to stamped microtracks of equal width and spacing (p < 0.05) and exhibited greater directional persistence on both 1D patterns compared to flat polystyrene (p < 0.05). Single-cell morphologies also differed significantly between flat and 1D patterns, with cells on 1D substrates exhibiting higher aspect ratios and less circularity (p < 0.05). This microfluidic platform could lead to automated quantification of single-cell migratory behavior due to the high predictability of hydrodynamic seeding and guided 1D migration, an important step to realizing the potential of microfluidic migration assays for drug screening and individualized medicine. Published under license by AIP Publishing.
- Versatile membrane-based microfluidic platform for in vitro drug diffusion testing mimicking in vivo environments(Elsevier, 2022) Arana-Alonso, S. (Sergio); Olaizola, C. (Claudia); Mitxelena-Iribarren, O. (Oihane); Mujika-Garmendia, M. (Maite)Mimicking the diffusion that drugs suffer through different body tissues before reaching their target is a challenge. In this work, a versatile membrane-based microfluidic platform was developed to allow for the identification of drugs that would keep their cytotoxic properties after diffusing through such a barrier. As an application case, this paper reports on a microfluidic device capable of mimicking the diffusion that free or encapsulated anticancer drugs would suffer in the intestine before reaching the bloodstream. It not only presents the successful fabrication results for the platform but also demonstrates the significant effect that the analyzed drugs have over the viability of osteosarcoma cells. This intestine-like microfluidic platform works as a tool to allow for the identification of drugs whose cytotoxic performance remains effective enough once they enter the bloodstream. Therefore, it allows for the prediction of the best treatment available for each patient in the battle against cancer.
- Different microfluidic environments for In vitro testing of lipid nanoparticles against osteosarcoma(MDPI, 2021-06-04) Arana-Alonso, S. (Sergio); Lizarbe-Sancha, S. (Sara); Campisi, J. (Jay); Mitxelena-Iribarren, O. (Oihane); Mujika-Garmendia, M. (Maite)The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment than traditional treatment methods. Although the combination of target therapy with nanotechnology created new hope for cancer treatment, methodological issues during in vitro validation of nanovehicles slowed their application. In the current work, the effect of methotrexate (MTX) encapsulated in different matrices was evaluated in a dynamic microfluidic platform. Effects on the viability of osteosarcoma cells in the presence of recirculation of cell media, free MTX and two types of blank and drug-containing nanoparticles were successfully assessed in different tumor-mimicking microenvironments. Encapsulated MTX was more effective than the equal dose free drug treatment, as cell death significantly increased under the recirculation of both types of drug-loaded nanoparticles in all concentrations. In fact, MTX-nanoparticles reduced cell population 50 times more than the free drug when 150-mu M drug dose was recirculated. Moreover, when compared to the equivalent free drug dose recirculation, cell number was reduced 60 and 100 points more under recirculation of each nanoparticle with a 15-mu M drug concentration. Thus, the results obtained with the microfluidic model present MTX-lipid nanoparticles as a promising and more effective therapy for pediatric osteosarcoma treatment than current treatment options.
- Design and fabrication of a microfluidic system with embedded circular channels for rotary cell culture(Wiley, 2023-07) Arana-Alonso, S. (Sergio); Alkorta, J. (Janire); Gracia, R. (Raquel); Zabalza, L. (Laura); Dupin, D. (Damien); Ruiz-Cabello, J. (Jesús); Mitxelena-Iribarren, O. (Oihane); Mujika-Garmendia, M. (Maite); Bujanda, X. (Xabier)The development of functional blood vessels is today a fundamental pillar in the evaluation of new therapies and diagnostic agents. This article describes the manufacture and subsequent functionalization, by means of cell culture, of a microfluidic device with a circular section. Its purpose is to simulate a blood vessel in order to test new treatments for pulmonary arterial hypertension. The manufacture was carried out using a process in which a wire with a circular section determines the dimensions of the channel. To fabricate the blood vessel, cells were seeded under rotary cell culture to obtain a homogeneous cell seeding in the inner wall of the devices. This is a simple and reproducible method that allows the generation of blood vessel models in vitro.
- TARTESSUS: A Customized Electrospun Drug Delivery System Loaded with Irinotecan for Local and Sustained Chemotherapy Release in Pancreatic Cancer(MDPI, 2023-02) Arana-Alonso, S. (Sergio); Astigarraga, M.(Malen); Padillo-Ruiz, J. (Javier); Mitxelena-Iribarren, O. (Oihane); Pereira, S. (Sheila); Calero-Castro, F.J.(Francisco José); Mujika-Garmendia, M. (Maite); Castillo-Tuñon, J.M.(Juan Manuel); Laga, I. (Iman); Cepeda-Franco, C. (Carmen)Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL)...
- Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment(Elsevier, 2019-01) Zabalo-Carrere, J. (Jon); Arana-Alonso, S. (Sergio); Mitxelena-Iribarren, O. (Oihane); Mujika-Garmendia, M. (Maite)Development of new targeted therapies is a challenge in the battle against cancer. Although a variety of treatments is currently available, there is no technique for rapidly evaluating the response of cancer patients to the drug. In this work, a microfluidic platform for the real-time simultaneous analysis of the success rate of different nanoparticle based chemotherapeutic drugs is presented. Based on a previous planar chamber and a reported sensitivity enhancing strategy, linear and cross shape microstructures were integrated into the chamber dome of the microfluidic polydimethylsiloxane and glass platform in order to provide a higher fluid mixing and treatment-cell interaction. Several methotrexate (MTX) based treatments (free MTX, MTX loaded Lecithin-PVA nanoparticles, MTX loaded Lecithin-Tween 80 nanoparticles) as well as their respective controls (cell media and both blank nanoparticles) were recirculated through the microchamber over an osteosarcoma cell monolayer. These nanovehicles reduced cell population to less than 20% (LEC-PVA nanoparticles) and 2.3% (LEC-Tween nanoparticles), demonstrating that nanoparticles are a promising target therapy for cancer treatment. Moreover, microstructured platforms demonstrated a higher efficacy in the drug-screening process: due to the liquid folding a higher amount of nanoparticles was internalized by the cells and, therefore, results were observed faster. In fact, the time required to reduce cell viability to the half was nearly a 75% faster. Furthermore, this microfluidic platform offers the capability to test up to five different drugs simultaneously, making it a powerful tool to evaluate the effect of multiple drugs and determine the most effective and personalized treatment.