Publications in the Year: 2018

Book Chapter

Vinhas, R, Fernandes AR, Baptista PV.  2018.  Molecular Diagnostics of Chronic Myeloid Leukemia - precision medicine via gold nanoparticles. In CDx and precision medicine for hematologic malignancies. (Il-Jin Kim, Ed.).:205-230.: PanStanford Publishing

Journal Article

Alves, PU, Vinhas R, Fernandes AR, Birol SZ, Trabzon L, Bernacka-Wojcik I, Igreja R, Lopes P, Baptista PV, Águas H, Fortunato E, Martins R.  2018.  Multifunctional microfluidic chip for optical nanoprobe based RNA detection – application to Chronic Myeloid Leukemia, 2018. Scientific Reports. 8(1):381. AbstractWebsite

Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.

Cordeiro, M, Otrelo-Cardoso AR, Svergun DI, Konarev PV, Lima JC, Santos-Silva T, Baptista PV.  2018.  Optical and Structural Characterization of a Chronic Myeloid Leukemia DNA Biosensor, 2018. ACS Chemical BiologyACS Chemical Biology. 13(5):1235-1242.: American Chemical Society AbstractWebsite

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Vinhas, R, Lourenco A, Santos S, Ribeiro P, Silva M, de Sousa AB, Baptista PV, Fernandes AR.  2018.  A double Philadelphia chromosome-positive chronic myeloid leukemia patient, co-expressing P210(BCR-ABL1) and P195(BCR-ABL1) isoforms. Haematologica. 103:E549-E552., Number 11 Abstract

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Daniela, P, Margarida F, Gabriela M, Catarina R‐R, V. BP, R. FA, Sónia B, Luísa CA, M. ACA, M. FL, S. BP.  2018.  Synthesis, Cytotoxicity Evaluation in Human Cell Lines and in Vitro DNA Interaction of a Hetero‐Arylidene‐9(10H)‐Anthrone, 2018. European Journal of Organic ChemistryEuropean Journal of Organic Chemistry. 2018(4):545-549.: Wiley-Blackwell AbstractWebsite

A new and never before reported hetero?arylidene?9(10H)?anthrone structure (4) was unexpectedly isolated on reaction of 1,2?dimethyl?3?ethylimidazolium iodide (2) and 9?anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally confirmed by X?ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed, indicating its applicability in biological systems. Compound 4 interacts with CT?DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity [Kb = 2.0?(±0.20)???105 m?1], which is 10?? higher than that described for doxorubicin [Kb = 3.2?(±0.23)???104 m?1]. Furthermore, compound 4 quenches the fluorescence emission of a GelRed?CT?DNA system with a quenching constant (KSV) of 3.3?(±0.3)???103 m?1 calculated by the Stern?Volmer equation.

Baptista, PV, McCusker MP, Carvalho A, Ferreira DA, Mohan NM, Martins M, Fernandes AR.  2018.  Nano-Strategies to Fight Multidrug Resistant Bacteria—“A Battle of the Titans”. Frontiers in Microbiology. 9:1441. AbstractWebsite

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.

Restani, RB, Pires RF, Tolmatcheva A, Cabral R, Baptista, Pedro V, Fernandes AR, Casimiro T, Bonifacio VDB, Aguiar-Ricardo A.  2018.  POxylated Dendrimer-Based Nano-in-Micro Dry Powder Formulations for Inhalation Chemotherapy. Chemistryopen. 7:772-779., Number 10 Abstract

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McCully, M, Conde J, V. Baptista P, Mullin M, Dalby MJ, Berry CC.  2018.  Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells, 2018/02/14. PLOS ONE. 13(2):e0192562-.: Public Library of Science 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.

Svahn, N, Moro AJ, Roma-Rodrigues C, Puttreddy R, Rissanen K, Baptista PV, Fernandes AR, Lima JC, Rodríguez L.  2018.  The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes. Chemistry – A European Journal. 24:14654-14667., Number 55 AbstractWebsite

Abstract A series of 4-ethynylaniline gold(I) complexes containing monophosphane (1,3,5-triaza-7-phosphaadamantane (pta; 2), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (3), and PR3, with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans-1,2-bis(diphenylphosphino)ethene (dppet; 8), 1,2-bis(diphenylphosphino)ethane (dppe; 9), and 1,3-bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2–10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC50=2.3 μm) compared with colorectal carcinoma and normal human fibroblasts (IC50>100 μm), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X-ray crystal structure determination allowed the identification of short N−H⋅⋅⋅π contacts as the main driving forces for the three-dimensional packing in these molecules.

Pedrosa, P, Mendes R, Cabral R, Martins LMDRS, Baptista PV, Fernandes AR.  2018.  Combination of chemotherapy and Au-nanoparticle photothermy in the visible light to tackle doxorubicin resistance in cancer cells. Scientific Reports. 8 Abstract

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Ribeiro, APC, Anbu S, Alegria ECBA, Fernandes AR, Baptista PV, Mendes R, Matias AS, Mendes M, Guedes da Silva MFC, Pombeiro AJL.  2018.  Evaluation of cell toxicity and DNA and protein binding of green synthesized silver nanoparticles, 2018. Biomedicine & Pharmacotherapy. 101:137-144. AbstractWebsite

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McCully, M, Conde J, Baptista PV, Mullin M, Dalby MJ, Berry CC.  2018.  Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells. Plos One. 13, Number 2 Abstract

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Baptista, PV.  2018.  Gold nanoprobe-based non-crosslinking hybridization for molecular diagnostics: an update. Expert Rev Mol Diagn. 18:767-773., Number 9 AbstractWebsite

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Report

Vinhas, R, Lourenço A, Santos S, Lemos M, Ribeiro P, de Sousa AB, Baptista PV, Fernandes AR.  2018.  A novel BCR-ABL1 mutation in a patient with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. :8589—8598.: OncoTargets and Therapy