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dos Santos, Renato, Ângelo Rocha, Ana Matias, Catarina Duarte, Isabel Sá-Nogueira, Nuno Lourenço, and João Paulo Borges. "Development of antimicrobial Ion Jelly fibers." RSC Advances 3 (2013): 24400-24405. Abstract

We report a method to obtain electrospun fibers based on ionic liquids and gelatin, exhibiting antimicrobial properties.

Soares, Paula I. P., Frederik Lochte, Coro Echeverria, Laura Pereira, Joana Coutinho, Isabel Ferreira, Carlos Novo, and João Paulo Borges. "Thermal and magnetic properties of iron oxide colloids: influence of surfactants." Nanotechnology 26 (2015): 425704. AbstractWebsite

Iron oxide nanoparticles (NPs) have been extensively studied in the last few decades for several biomedical applications such as magnetic resonance imaging, magnetic drug delivery and hyperthermia. Hyperthermia is a technique used for cancer treatment which consists in inducing a temperature of about 41–45 °C in cancerous cells through magnetic NPs and an external magnetic field. Chemical precipitation was used to produce iron oxide NPs 9 nm in size coated with oleic acid and trisodium citrate. The influence of both stabilizers on the heating ability and in vitro cytotoxicity of the produced iron oxide NPs was assessed. Physicochemical characterization of the samples confirmed that the used surfactants do not change the particles' average size and that the presence of the surfactants has a strong effect on both the magnetic properties and the heating ability. The heating ability of Fe3O4 NPs shows a proportional increase with the increase of iron concentration, although when coated with trisodium citrate or oleic acid the heating ability decreases. Cytotoxicity assays demonstrated that both pristine and trisodium citrate Fe3O4 samples do not reduce cell viability. However, oleic acid Fe3O4 strongly reduces cell viability, more drastically in the SaOs-2 cell line. The produced iron oxide NPs are suitable for cancer hyperthermia treatment and the use of a surfactant brings great advantages concerning the dispersion of NPs, also allowing better control of the hyperthermia temperature.

Soares, Paula I. P., Coro Echeverria, Ana Catarina Baptista, Carlos João, Susete Fernandes, Ana Almeida, Jorge Carvalho Silva, Maria Helena Godinho, and João Paulo Borges. "Hybrid polysaccharide-based systems for biomedical applications." In Hybrid Polymer Composite Materials: Applications, edited by Manju Kumari Thakur, Vijay Kumar Thakur and Asokan Pappu, 107-149. USA: Woodhead Publishing, Elsevier, 2017. Abstract

Hybrid materials have been widely studied for structural applications. Polysaccharide-based fibers, especially cellulosic fibers, have been explored in the last two decades as substitutes of the traditional reinforcements made of glass or carbon fibers due to their mechanical properties. However, their biocompatibility, biodegradability, and chemistry have attracted the researchers and new developments in the field of smart and functional materials arise in diverse applications. This chapter will focus on the biomedical applications of polysaccharide-based smart and functional materials, namely those concerning biosensors and actuators, theranostic systems, and tissue-engineering applications. Special attention will be given to cellulose- and chitin/chitosan-based hybrid materials because these are the two most abundant polysaccharides and probably the most promising for the development of hybrid materials for biomedical applications. Biomimetic strategies for the development of smart and functional hybrid materials will also be highlighted.

Soares, Paula I. P., César Laia, Alexandra Carvalho, Laura Pereira, Joana Coutinho, Isabel Ferreira, Carlos Novo, and João Paulo Borges. "Iron oxide nanoparticles stabilized with a bilayer of oleic acid for magnetic hyperthermia and MRI applications." Applied Surface Science 383 (2016): 240-247. AbstractWebsite

Iron oxide nanoparticles (Fe3O4, IONPs) are promising candidates for several biomedical applications such as magnetic hyperthermia and as contrast agents for magnetic resonance imaging (MRI). However, their colloidal stability in physiological conditions hinders their application requiring the use of biocompatible surfactant agents. The present investigation focuses on obtaining highly stable IONPs, stabilized by the presence of an oleic acid bilayer. Critical aspects such as oleic acid concentration and pH were optimized to ensure maximum stability. NPs composed of an iron oxide core with an average diameter of 9 nm measured using transmission electron microscopy (TEM) form agglomerates with an hydrodynamic diameter of around 170 nm when dispersed in water in the presence of an oleic acid bilayer, remaining stable (zeta potential of −120 mV). Magnetic hyperthermia and the relaxivities measurements show high efficiency at neutral pH which enables their use for both magnetic hyperthermia and MRI.

Soares, Paula I. P., Isabel Ferreira, and João Paulo Borges. "Application of Hyperthermia for Cancer Treatment: Recent Patents Review." In Topics in Anti-Cancer Research, Vol. 3, edited by Atta-ur-Rahman and Khurshid Zaman, 342-383. Bentham Science Publishers, 2014. Abstract

Cancer is one of the main causes of death in the world and its incidence increases every day. Current treatments are insufficient and present many breaches. Hyperthermia is an old concept and was early established as a cancer treatment option, mainly in superficial cancers. More recently, the concept of intracellular hyperthermia emerged wherein magnetic particles are concentrated at the tumor site and remotely heated using an applied magnetic field to achieve hyperthermic temperatures (42-45ºC). Many patents have been registered in this area since the year 2000. This chapter presents the most relevant information organized in two main categories according to the use or not of nanotechnology. The patents without nanotechnology were divided into the following subcategories: 1) external Radio-Frequency devices; 2) hyperthermic perfusion; 3) frequency enhancers; 4) applying heat to the target site using a catheter; and 5) injection of magnetic and ferroelectric particles. The patents with nanotechnology were divided into three subcategories: 1) hyperthermia devices; 2) nanoparticles; and 3) nanostructures. The use of magnetic nanoparticles is a very promising treatment approach since it may be used for diagnostic and treatment. Magnetic nanoparticle could be applied to detect and diagnose the tumor and to carry a pharmacological active drug to be delivered in the tumor site or apply hyperthermia through an external magnetic field.

Soares, Paula I. P., Ana Alves, Laura Pereira, Joana Coutinho, Isabel Ferreira, Carlos Novo, and João Paulo Borges. "Effects of surfactants on the magnetic properties of iron oxide colloids." Journal of Colloid and Interface Science 419 (2014): 46-51. AbstractWebsite

Iron oxide nanoparticles are having been extensively investigated for several biomedical applications such as hyperthermia and magnetic resonance imaging. However, one of the biggest problems of these nanoparticles is their aggregation.
Taking this into account, in this study the influence of three different surfactants (oleic acid, sodium citrate and Triton X-100) each one with various concentrations in the colloidal solutions stability was analyzed by using a rapid and facile method, the variation in the optical absorbance along time.
The synthesized nanoparticles through chemical precipitation showed an average size of 9 nm and a narrow size distribution. X-ray diffraction pattern and Fourier Transform Infrared analysis confirmed the presence of pure magnetite. SQUID measurements showed superparamagnetic properties with a blocking temperature around 155 K. In addition it was observed that neither sodium citrate nor Triton X-100 influences the magnetic properties of the nanoparticles. On the other hand, oleic acid in a concentration of 64 mM decreases the saturation magnetization from 67 to 45 emu/g. Oleic acid exhibits a good performance as stabilizer of the iron oxide nanoparticles in an aqueous solution for 24 h, for concentrations that lead to the formation of the double layer.

Soares, Paula I. P., Joana Romão, Ricardo Matos, Jorge Carvalho Silva, and João Paulo Borges. "Design and engineering of magneto-responsive devices for cancer theranostics: Nano to macro perspective." Progress in Materials Science 116 (2021): 100742. AbstractWebsite

Design, research, and development of new and improved smart multifunctional devices is one of the main topics in the advanced functional materials agenda for the next decade. Smart materials that can be triggered by external stimuli are seen with high potential for innovative treatments and improved drug delivery systems by regulatory agencies like the FDA and EMA. The incorporation of magnetic nanostructures into complex systems produces multifunctional devices that can be spatiotemporally controlled by an external magnetic field. These magneto-responsive devices can be used for a multitude of biomedical applications, from diagnostic to the treatment of tumors, and are actively being developed and tested for cancer theranostics. Herein, we review the development of magneto-responsive devices for cancer theranostics, starting from the most straightforward architecture, single nanoparticles. We give some theoretical concepts about the design and production of such systems while providing a critical review of applications in clinical practice. Naturally, the review evolves to more complex architectures, from one-dimensional to three-dimensional magneto-responsive systems, demonstrating higher complexity and multifunctionality, and consequently, higher interest for clinical practice. The review ends with the main challenges in the design and engineering of magneto-responsive devices for cancer theranostics and future trends in this biomedical field.

Soares, Paula I. P., Diana Machado, César Laia, Laura Pereira, Joana Coutinho, Isabel Ferreira, Carlos Novo, and João Paulo Borges. "Thermal and magnetic properties of chitosan-iron oxide nanoparticles." Carbohydrate polymers 149 (2016): 382-390. AbstractWebsite

Chitosan is a biopolymer widely used for biomedical applications such as drug delivery systems, wound healing, and tissue engineering. Chitosan can be used as coating for other types of materials such as iron oxide nanoparticles, improving its biocompatibility while extending its range of applications.
In this work iron oxide nanoparticles (Fe3O4 NPs) produced by chemical precipitation and thermal decomposition and coated with chitosan with different molecular weights were studied. Basic characterization on bare and chitosan-Fe3O4 NPs was performed demonstrating that chitosan does not affect the crystallinity, chemical composition, and superparamagnetic properties of the Fe3O4 NPs, and also the incorporation of Fe3O4 NPs into chitosan nanoparticles increases the later hydrodynamic diameter without compromising its physical and chemical properties. The nano-composite was tested for magnetic hyperthermia by applying an alternating current magnetic field to the samples demonstrating that the heating ability of the Fe3O4 NPs was not significantly affected by chitosan.

Soares, Paula I. P., Isabel Ferreira, Rui Igreja, Carlos Novo, and João Paulo Borges. "Application of Hyperthermia for Cancer Treatment: Recent Patents Review." Recent Patents on Anti-Cancer Drug Discovery 7 (2012): 64-73. AbstractWebsite

Cancer is one of the main causes of death in the world and its incidence increases every day. Current treatments are insufficient and present many breaches. Hyperthermia is an old concept and since early it was established as a cancer treatment option, mainly in superficial cancers. More recently the concept of intracellular hyperthermia emerged wherein magnetic particles are concentrated at the tumor site and remotely heated using an applied magnetic field to achieve hyperthermic temperatures (42-45°C). Many patents have been registered in this area since the year 2000. This review presents the most relevant information, organizing them according to the hyperthermic method used: 1) external Radio- Frequency devices; 2) hyperthermic perfusion; 3) frequency enhancers; 4) apply heating to the target site using a catheter; 5) injection of magnetic and ferroelectric particles; 6) injection of magnetic nanoparticles that may carry a pharmacological active drug. The use of magnetic nanoparticles is a very promising treatment approach since it may be used for diagnostic and treatment. An ideal magnetic nanoparticle would be able to detect and diagnose the tumor, carry a pharmacological active drug to be delivered in the tumor site, apply hyperthermia through an external magnetic field and allow treatment monitoring by magnetic resonance imaging.

Soares, Paula I. P., Ana Isabel Sousa, Isabel Ferreira, Carlos Novo, and João Borges Borges. "Towards the development of multifunctional chitosan-based iron oxide nanoparticles: Optimization and modelling of doxorubicin release." Carbohydrate Polymers 153 (2016): 212-221. AbstractWebsite

In the present work composite nanoparticles with a magnetic core and a chitosan-based shell were produced as drug delivery systems for doxorubicin (DOX). The results show that composite nanoparticles with a hydrodynamic diameter within the nanometric range are able to encapsulate more DOX than polymeric nanoparticles alone corresponding also to a higher drug release. Moreover the synthesis method of the iron oxide nanoparticles influences the total amount of DOX released and a high content of iron oxide nanoparticles inhibits DOX release. The modelling of the experimental results revealed a release mechanism dominated by Fickian diffusion.

Soares, Paula I. P., Ana Isabel Sousa, Jorge Carvalho Silva, Isabel Ferreira, Carlos Novo, and João Paulo Borges. "Chitosan-based nanoparticles as drug delivery systems for doxorubicin: optimization and modelling." Carbohydrate polymers 147 (2016): 304-312. AbstractWebsite

In the present work, two drug delivery systems were produced by encapsulating doxorubicin into chitosan and O-HTCC (ammonium-quaternary derivative of chitosan) nanoparticles. The results show that doxorubicin release is independent of the molecular weight and is higher at acidic pH (4.5) than at physiological pH. NPs with an average hydrodynamic diameter bellow 200 nm are able to encapsulate up to 70% and 50% of doxorubicin in the case of chitosan and O-HTCC nanoparticles, respectively. O-HTCC nanoparticles led to a higher amount of doxorubicin released than chitosan nanoparticles, for the same experimental conditions, although the release mechanism was not altered. A burst effect occurs within the first hours of release, reaching a plateau after 24 h. Fitting mathematical models to the experimental data led to a concordant release mechanism between most samples, indicating an anomalous or mixed release, which is in agreement with the swelling behavior of chitosan described in the literature.

Soares, Paula I. P., Sérgio Dias, Carlos Novo, Isabel Ferreira, and João Paulo Borges. "Doxorubicin vs. ladirubicin: methods for improving osteosarcoma treatment." Mini reviews in medicinal chemistry 12 (2012): 1239-1249. AbstractWebsite

Osteosarcoma is the most common primary bone tumor in children and adolescents, with a 5-year disease free survival rate of 70%. Current chemotherapy regimens comprise a group of chemotherapeutic agents in which doxorubicin is included. However, tumor resistance to anthracyclines and cardiotoxicity are limiting factors for its usage. Liposomal formulations of doxorubicin improve its anti-cancer effects but are still insufficient. The research in this area has lead to the production of anthracyclines analogues, such as ladirubicin, the leading compound of alkylcyclines. This new anticancer agent has shown promising results in vivo and in vitro, being effective against osteosarcoma cell lines, including those with a multidrug resistant phenotype. In phase I clinical trials, this molecule caused mild side effects and did not induce significant cardiotoxicity at doses ranging from 1 to 16 mg/m2, resulting in a peak plasma concentration (Cmax) ranging from 0.5 to 1.5 μM. The recommended doses for phase II studies were 12 and 14 mg/m2 in heavily and minimally pretreated/non-pretreated patients, respectively. Phase II clinical trials in ovary, breast, colorectal cancer, NSCLC and malignant melanoma are underway. Given the improved molecular targeting efficacy of these new compounds, ongoing approaches have sought to improve drug delivery systems, to improve treatment efficacy while reducing systemic toxicity. The combination of these two approaches may be a good start for the discovery of new treatment for osteosarcoma.

Strohmeier, P., C. Honnet, H. Perner-Wilson, M. Teyssier, B. Fruchard, Ana Catarina Baptista, and J. Steimle. Demo of PolySense: How to Make Electrically Functional Textiles In CHI Conference on Human Factors in Computing Systems., 2020. Abstract

We demonstrate a simple and accessible method for enhancing textiles with custom piezo-resistive properties. Based on in-situ polymerization, our method offers seamless integration at the material level, preserving a textile's haptic and mechanical properties. We demonstrate how to enhance a wide set of fabrics and yarns using only readily available tools. During each demo session, conference attendees may bring textile samples which will be polymerized in a shared batch. Attendees may keep these samples. While the polymerization is happening, attendees can inspect pre-made samples and explore how these might be integrated in functional circuits. Examples objects created using polymerization include rapid manufacturing of on-body interfaces, tie-dyed motion-capture clothing, and zippers that act as potentiometers.