Publications

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2020
Antiproliferative Activities of Diimine-Based Mixed Ligand Copper(II) Complexes, Kordestani, N., Rudbari H. A., Fernandes A. R., Raposo L. R., Baptista P. V., Ferreira D., Bruno G., Bella G., Scopelliti R., Braun J. D., Herbert D. E., and Blacque O. , ACS Comb Sci, Volume 22, Number 2, p.89-99, (2020) AbstractWebsite

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Exploiting the antiproliferative potential of spiropyrazoline oxindoles in a human ovarian cancer cell line, Raposo, L. R., Silva A., Silva D., Roma-Rodrigues C., Espadinha M., Baptista P. V., Santos M. M. M., and Fernandes A. R. , Bioorg Med Chem, Volume 30, p.115880, (2020) AbstractWebsite

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Fast Prototyping Microfluidics: Integrating Droplet Digital Lamp for Absolute Quantification of Cancer Biomarkers, Oliveira, B., Veigas B., Fernandes A. R., Águas H., Martins R., Fortunato E., and Baptista P. V. , Sensors (Basel), Volume 20, Number 6, (2020) AbstractWebsite

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Gene Therapy in Cancer Treatment: Why Go Nano?, Roma-Rodrigues, C., Rivas-García L., Baptista P. V., and Fernandes A. R. , Pharmaceutics, Volume 12, Number 3, (2020) AbstractWebsite

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Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics, Ferreira, D., Fontinha D., Martins C., Pires D., Fernandes A. R., and Baptista P. V. , Molecules, Volume 25, Number 15, (2020) AbstractWebsite

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The Intracellular Number of Magnetic Nanoparticles Modulates the Apoptotic Death Pathway after Magnetic Hyperthermia Treatment, Beola, L., Asín L., Roma-Rodrigues C., Fernández-Afonso Y., Fratila R. M., Serantes D., Ruta S., Chantrell R. W., Fernandes A. R., Baptista P. V., de la Fuente J. M., Grazú V., and Gutiérrez L. , ACS Appl Mater Interfaces, Volume 12, Number 39, p.43474-43487, (2020) AbstractWebsite

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Synthesis of new hetero-arylidene-9(10H)-anthrone derivatives and their biological evaluation, Roma-Rodrigues, C., Malta G., Peixoto D., Ferreira LM, Baptista P. V., Fernandes A. R., and Branco P. S. , Bioorg Chem, Volume 99, p.103849, (2020) AbstractWebsite

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Tackling Multidrug Resistance in Streptococci - From Novel Biotherapeutic Strategies to Nanomedicines, Alves-Barroco, C., Rivas-García L., Fernandes A. R., and Baptista P. V. , Front Microbiol, Volume 11, p.579916, (2020) AbstractWebsite

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Water safety screening via multiplex LAMP-Au-nanoprobe integrated approach, Oliveira, B. B., Veigas B., Carlos F. F., Sánchez-Melsió A., Balcázar J. L., Borrego C. M., and Baptista P. V. , Sci Total Environ, Volume 741, p.140447, (2020) AbstractWebsite

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2019
GLUT1 and GLUT3 involvement in anthocyanin gastric transport- Nanobased targeted approach, Oliveira, Hélder, Roma-Rodrigues Catarina, Santos Ana, Veigas Bruno, Brás Natércia, Faria Ana, Calhau Conceição, de Freitas Victor, Baptista Pedro V., Mateus Nuno, Fernandes Alexandra R., and Fernandes Iva , Scientific Reports, 2019, Volume 9, Issue 1, p.789, (2019) AbstractWebsite

Anthocyanins may protect against a myriad of human diseases. However few studies have been conducted to evaluate their bioavailability so their absorption mechanism remains unclear. This study aimed to evaluate the role of two glucose transporters (GLUT1 and GLUT3) in anthocyanins absorption in the human gastric epithelial cells (MKN-28) by using gold nanoparticles to silence these transporters. Anthocyanins were purified from purple fleshed sweet potatoes and grape skin. Silencing of GLUT1 and/or GLUT3 mRNA was performed by adding AuNP@GLUT1 and/or AuNP@GLUT3 to MKN-28 cells. Downregulation of mRNA expression occurred concomitantly with the reduction in protein expression. Malvidin-3-O-glucoside (Mv3glc) transport was reduced in the presence of either AuNP@GLUT1 and AuNP@GLUT3, and when both transporters were blocked simultaneously. Peonidin-3-(6′-hydroxybenzoyl)-sophoroside-5-glucoside (Pn3HBsoph5glc) and Peonidin-3-(6′-hydroxybenzoyl-6″-caffeoyl)-sophoroside-5-glucoside (Pn3HBCsoph5glc) were assayed to verify the effect of the sugar moiety esterification at glucose B in transporter binding. Both pigments were transported with a lower transport efficiency compared to Mv3glc, probably due to steric hindrance of the more complex structures. Interestingly, for Pn3HBCsoph5glc although the only free glucose is at C5 and the inhibitory effect of the nanoparticles was also observed, reinforcing the importance of glucose on the transport regardless of its position or substitution pattern. The results support the involvement of GLUT1 and GLUT3 in the gastric absorption of anthocyanins.

Nanotheranostics Targeting the Tumor Microenvironment, Roma-Rodrigues, Catarina, Pombo Inês, Raposo Luís, Pedrosa Pedro, Fernandes Alexandra R., and Baptista Pedro V. , Front. Bioeng. Biotechnol., 2019, Volume 7, p.197, (2019) AbstractWebsite

Cancer is considered the most aggressive malignancy to humans, and definitely the major cause of death worldwide. Despite the different and heterogenous presentation of the disease, there are pivotal cell elements involved in proliferation, differentiation, and immortalization, and ultimately the capability to evade treatment strategies. This is of utmost relevance when we are just beginning to grasp the complexity of the tumor environment and the molecular “evolution” within. The tumor micro-environment (TME) is thought to provide for differentiation niches for clonal development that results in tremendous cancer heterogeneity. To date, conventional cancer therapeutic strategies against cancer are failing to tackle the intricate interplay of actors within the TME. Nanomedicine has been proposing innovative strategies to tackle this TME and the cancer cells that simultaneously provide for biodistribution and/or assessment of action. These nanotheranostics systems are usually multi-functional nanosystems capable to carry and deliver active cargo to the site of interest and provide diagnostics capability, enabling early detection, and destruction of cancer cells in a more selective way. Some of the most promising multifunctional nanosystems are based on gold nanoparticles, whose physic-chemical properties have prompt for the development of multifunctional, responsive nanomedicines suitable for combinatory therapy and theranostics. Herein, we shall focus on the recent developments relying on the properties of gold nanoparticles as the basis for nanotheranostics systems against the heterogeneity within the TME.

Antibody modified gold nanoparticles for fast colorimetric screening of rheumatoid arthritis, Veigas, B., Matias A., Calmeiro T., Fortunato E., Fernandes A. R., and Baptista P. V. , Analyst, Volume 144, Number 11, p.3613-3619, (2019) AbstractWebsite

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Antiproliferative activity of heterometallic sodium and potassium-dioxidovanadium(V) polymers, Sutradhar, M., Alegria E. C. B. A., Ferretti F., Raposo L. R., Guedes da Silva M. F. C., Baptista P. V., Fernandes A. R., and Pombeiro A. J. L. , J Inorg Biochem, Volume 200, p.110811, (2019) AbstractWebsite

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Counteracting the effect of leukemia exosomes by antiangiogenic gold nanoparticles, Roma-Rodrigues, C., Fernandes A. R., and Baptista P. V. , Int J Nanomedicine, Volume 14, p.6843-6854, (2019) AbstractWebsite

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Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids., Jesus, Ana R., Soromenho Mario R. C., Raposo Luis R., Esperanca Jose M. S. S., Baptista Pedro V., Fernandes Alexandra R., and Reis Patricia M. , European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, (2019) Abstract

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Ionic Liquids and Salts from Ibuprofen as Promising Innovative Formulations of an Old Drug, Santos, Miguel M., Raposo Luís R., Carrera Gonçalo V. S. M., Costa Alexandra, Dionísio Madalena, Baptista Pedro V., Fernandes Alexandra R., and Branco Luís C. , ChemMedChem, Volume 14, Number 9, p.907-911, (2019) AbstractWebsite

Abstract Herein we report the synthesis of novel ionic liquids (ILs) and organic salts by combining ibuprofen as anion with ammonium, imidazolium, or pyridinium cations. The methodology consists of an acid–base reaction of neutral ibuprofen with cation hydroxides, which were previously prepared by anion exchange from the corresponding halide salts with Amberlyst A-26(OH). In comparison with the parent drug, these organic salts display higher solubility in water and biological fluids and a smaller degree of polymorphism, which in some cases was completely eliminated. With the exception of [C16Pyr][Ibu] and [N1,1,2,2OH1][Ibu], the prepared salts did not affect the viability of normal human dermal fibroblasts or ovarian carcinoma (A2780) cells. Therefore, these ibuprofen-based ionic liquids may be very promising lead candidates for the development of effective formulations of this drug.

Occurrence of non-toxic bioemulsifiers during polyhydroxyalkanoate production by Pseudomonas strains valorizing crude glycerol by-product, Kourmentza, C., Araujo D., Sevrin C., Roma-Rodriques C., Lia Ferreira J., Freitas F., Dionisio M., Baptista P. V., Fernandes A. R., Grandfils C., and Reis M. A. M. , Bioresour Technol, Volume 281, p.31-40, (2019) AbstractWebsite

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Paper-Based SERS Platform for One-Step Screening of Tetracycline in Milk, Marques, A., Veigas B., Araújo A., Pagará B., Baptista P. V., Águas H., Martins R., and Fortunato E. , Sci Rep, Volume 9, Number 1, p.17922, (2019) AbstractWebsite

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Structural aspects of a trimetallic CuII derivative: cytotoxicity and anti-proliferative activity on human cancer cell lines, Das, Kuheli, Datta Amitabha, Massera Chiara, Roma-Rodrigues Catarina, Barroso Mariana, Baptista Pedro V., and Fernandes Alexandra R. , Journal of Coordination Chemistry, Volume 72, Number 5-7, p.920-940, (2019) AbstractWebsite

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Structural characterization and biological properties of silver(I) tris(pyrazolyl)methane sulfonate, Almeida, J., Roma-Rodrigues C., Mahmoud A. G., Guedes da Silva M. F. C., Pombeiro A. J. L., Martins D.RS L. M., Baptista P. V., and Fernandes A. R. , J Inorg Biochem, Volume 199, p.110789, (2019) AbstractWebsite

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Targeting Cancer Resistance via Multifunctional Gold Nanoparticles, Pedrosa, Pedro, Corvo Luísa M., Ferreira-Silva Margarida, Martins Pedro, Carvalheiro Manuela Colla, Costa Pedro M., Martins Carla, Martins L. M. D. R. S., Baptista Pedro V., and Fernandes Alexandra R. , International Journal of Molecular Sciences, Volume 20, Number 21, (2019) AbstractWebsite

Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.

Targeting Cancer Resistance via Multifunctional Gold Nanoparticles, Pedrosa, P., Corvo M. L., Ferreira-Silva M., Martins P., Carvalheiro MC, Costa P. M., Martins C., Martins D.RS L. M., Baptista P. V., and Fernandes A. R. , Int J Mol Sci, Volume 20, Number 21, (2019) AbstractWebsite

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Targeting Tumor Microenvironment for Cancer Therapy, Roma-Rodrigues, C., Mendes R., Baptista P. V., and Fernandes A. R. , Int J Mol Sci, Volume 20, Number 4, (2019) AbstractWebsite

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2018
Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells, McCully, Mark, Conde João, V. Baptista Pedro, Mullin Margaret, Dalby Matthew J., and Berry Catherine C. , PLOS ONE, 2018/02/14, Volume 13, Issue 2, p.e0192562 - , (2018) AbstractWebsite

Mesenchymal stem cells are multipotent adult stem cells capable of generating bone, cartilage and fat, and are thus currently being exploited for regenerative medicine. When considering osteogenesis, developments have been made with regards to chemical induction (e.g. differentiation media) and physical induction (e.g. material stiffness, nanotopography), targeting established early transcription factors or regulators such as runx2 or bone morphogenic proteins and promoting increased numbers of cells committing to osteo-specific differentiation. Recent research highlighted the involvement of microRNAs in lineage commitment and terminal differentiation. Herein, gold nanoparticles that confer stability to short single stranded RNAs were used to deliver MiR-31 antagomiRs to both pre-osteoblastic cells and primary human MSCs in vitro. Results showed that blocking miR-31 led to an increase in osterix protein in both cell types at day 7, with an increase in osteocalcin at day 21, suggesting MSC osteogenesis. In addition, it was noted that antagomiR sequence direction was important, with the 5 prime reading direction proving more effective than the 3 prime. This study highlights the potential that miRNA antagomiR-tagged nanoparticles offer as novel therapeutics in regenerative medicine.