Nanogold-based materials in medicine: from their origins to their future.

The properties of gold-based materials have been explored for centuries in several research fields, including medicine. Multiple published production methods for gold nanoparticles (AuNPs) have shown that the physicochemical and optical properties of AuNPs depend on the production method used. These different AuNP properties have allowed exploration of their usefulness in countless distinct biomedical applications over the last few years. Here we present an extensive overview of the most commonly used AuNP production methods, the resulting distinct properties of the AuNPs and the potential application of these AuNPs in diagnostic and therapeutic approaches in biomedicine

Metastatic Myoepithelial Carcinoma Ex Pleomorphic Adenoma of the Sublingual Salivary Gland

Myoepithelial carcinoma ex pleomorphic adenoma is a very rare malignant neoplasm of the salivary gland. Owing to its rarity, its clinical features and treatment are not well characterized. We describe a case of a patient who was referred to our department with a six-month history of a bulge on the right side of the floor of the mouth and a submandibular mass with progressive enlargement. The mass was resected, and an elective level I neck dissection was performed. Histological examination revealed myoepithelial carcinoma ex pleomorphic adenoma of the sublingual salivary gland. Thoracic computed tomography and biopsy revealed lung metastases. The patient died two years after the diagnosisinfo:eu-repo/semantics/publishedVersio

A Step Forward in Breast Cancer Research: Gold Nanoparticles as Photothermal Therapy Enhancers

Gold nanoparticles (AuNPs) have been widely used and characterized for multiple biomedical applications, including the enhancement of photothermal therapy (PTT). AuNPs present a particular plasmon resonance band and are able to convert the absorbed optical radiation into heat, which validates their use in PTT. Several production methods have already been proposed for the synthesis of AuNPs, allowing to optimize the particles' morphology, size and optical properties. However, the production methods commonly used are frequently associated with the use of toxic reagents such as Cetyltrimethylammonium bromide, which presents some concerns for clinical applications. Herein, it is proposed a novel AuNPs' core synthesis method using tetrachloroauric acid and a mixture of reducing agents, later on coated with a combination of hyaluronic and oleic acids. The coating here represents a potential improvement of AuNPs biocompatibility, biodegradability and lifetime, while simultaneously potentiating the attachment towards specific ligands, such as the CD44 receptor, to develop more localized and highly selective tools. The produced functionalized nanoparticles were characterized by Dynamic Light Scattering, Microscopy Techniques and Spectroscopy, showing diameter sizes under 350 nm, polydispersity index smaller than 0.4 and enhanced absorbance in the Near Infrared (NIR, 650 to 900 nm) range. Moreover, the AuNPs safety and efficacy were preliminarily assessed in vitro using breast cancer cell lines. No toxicity was observed by MTT assay, both in breast cancer cell lines, and red blood cells. The irradiation process was proved to be safe; however, when combined with the AuNPs administration, it resulted in a significant reduction of cell viability for some of the breast cell lines tested. Thus, the results highlight the potential of the proposed system for some type of tumors, even though further tests are required to better understand the mechanisms behind the obtained results

The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment.

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer

Functionalized polyester-based materials as UV curable adhesives

UV curable adhesives offer major advantages in comparison to other polymeric based adhesive systems, such as fast-curing rate and control of the polymerization heat evolution, being ideal for application on damaged tissues. Herein, functionalized polymers were prepared by modifying polycaprolactone diol (PCL) with an isocyanate-functional unsaturated acrylic ester, Laromer® 9000, using two different proportions. These functionalized materials were chemically/physically characterized and, after the addition of a biocompatible photoinitiator (Irgacure® 2959), were crosslinked by UV light irradiation. Such procedure allows the obtention of flexible transparent films. Films’ properties such as swelling, hydrolytic degradation, thermal stability, surface energy and adhesive capacity were evaluated. Furthermore, to assess the applicability of the films in biomedical applications, their haemocompatibility and biocompatibility were determined using human dermal fibroblasts as model.info:eu-repo/semantics/acceptedVersio

N-(5-Amino-9H-benzo[a]phenoxazin-9-ylidene)propan-1-aminium chlorides as antifungal agents and NIR fluorescence probes

The search for benzo[a]phenoxazines, Nile Blue derivatives, with high antifungal activity and cell labelling capacity based on our previously published works in this type of compounds, led us to the design of compounds with specific substituents in the polycyclic system. Thus, in the present work, four new benzo[a]phenoxazinium chlorides, possessing at the 5-position amino or (3-aminopropyl) amino groups and at the 9-position propylamino or dipropylamino groups, were synthesized. Another analogue, with (3-aminopropyl) amino group at 5-position, ethyl amino group at 9-position and a methyl group at 10-position of the polycyclic system was also synthesized for comparison in the studies performed. Fundamental photophysics (absorption and fluorescent emission) was carried out in absolute ethanol, water, and other aqueous solutions of different pH values, relevant for the potential biological applications of these compounds. The antiproliferative activity of the synthesized benzo[a]phenoxazinium chlorides was determined using Saccharomyces cerevisiae PYCC 4072 and the microdilution method described for antifungal susceptibility tests in yeast. All compounds revealed antifungal activity, being the most active the one possessing an amino group at 5-position and an aminopropyl group at 9-position. The potential as fluorescent probes were evaluated by fluorescence microscopy, using S. cerevisae as a model system of eukaryotic cells, and it was found that the benzo[a]phenoxazinium chlorides stained the cells with preferential accumulation that seems to appear at the vacuolar membrane and/or the perinuclear membrane of the endoplasmatic reticulum.Thanks are due to Fundação para a Ciência e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU for financial support through the research centres CQ/UM (UID/QUI/0686/2019 and UIDB/00686/2020) and CBMA (PEst-OE/BIA/UI4050/2019 and UID/BIA/04050/2020), as well as a PhD grant to J. C. F. (SFRH/BD/133207/2017). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network (PTNMR) and is partially supported by Infrastructure Project No. 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC)

Gold nanoparticles as a part of a photothermal therapy system.

Introduction Photothermal therapy (PTT) is attracting increased attention for the treatment of superficial localized tumors, relying on the induction of local hyperthermia of tumor cells upon their irradiation with light beams1. PTT efficacy depends, however, on the heat generated and, on the depth reached by the light. Some strategies to improve PTT efficacy includes the use of the near infrared (NIR, 650 to 900 nm) radiation to enhance the penetration depth of the light, combined with gold nanoparticles (AuNPs) to enhance the photothermal effect2. Experimental Methods Core AuNPs were synthesized by a novel method using tetrachloroauric acid and a mixture of reducing agents, and subsequently coated with a combination of hyaluronic and oleic acids, for improving the NPs biocompatibility, biodegradability, and lifetime. This coating also promotes the binding of specific cell receptors of the tumor cells. The particles were physico-chemically characterized, and in vitro and in vivo tests were carried out in breast cancer models to assess their safety and efficacy, when applied alone or combined with NIR irradiation3. Results and Discussion AuNPs presented a predominant spherical morphology with sizes under 350 nm, polydispersity index lower than 0.4 and enhanced absorbance in the NIR. The particles showed no toxicity in vitro and promising efficacy in vivo when administering the NPs in situ and later irradiating them externally. Histopathological analysis of tumors treated with both AuNPs and laser irradiation showed the presence of necrosis in most of the tumors and no effect or practically absence in healthy surrounding cells, which are very encouraging outcomes. Conclusion The results are promising, however, there is still room for improving the system, namely by reducing even more the invasiveness of the treatment through the combined use of aerogels structures. Aerogel’s unique properties4 make them ideal candidates to minimize the exposure of healthy tissues to laser radiation, acting as light and thermal insulators, as well as to incorporate the nanoparticles into their skeletal structure and thus potentiating a topical application of the particles. For these reasons, some exploratory methods were carried to produce and design aerogels structures for PTT applications