By Type: Journal Article

Veigas, Bruno, Elvira Fortunato, and Pedro V. Baptista. "Field Effect Sensors for Nucleic Acid Detection: Recent Advances and Future Perspectives." Sensors 15 (2015): 10380-10398. Abstract

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Veigas, Bruno, Pedro Pedrosa, Fabio F. Carlos, Liliana Mancio-Silva, Ana Rita Grosso, Elvira Fortunato, Maria M. Mota, and Pedro V. Baptista. "One nanoprobe, two pathogens: gold nanoprobes multiplexing for point-of-care." Journal of Nanobiotechnology 13 (2015). Abstract

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Mendo, Ana Soraia, Sara Figueiredo, Catarina Roma-Rodrigues, Paula A. Videira, Zhen Ma, Mário Diniz, Miguel Larguinho, Pedro Costa, João C. Lima, Armando J. L. Pombeiro, Pedro V. Baptista, and Alexandra R. Fernandes. "Characterization of antiproliferative potential and biological targets of a copper compound containing 4'-phenyl terpyridine." JBIC Journal of Biological Inorganic Chemistry 2 (2015): 935-948. AbstractWebsite

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

Vinhas, Raquel, Milton Cordeiro, Fábio Carlos, Soraia Mendo, Alexandra Fernandes, Sara Figueiredo, and Pedro Baptista. "Gold nanoparticle-based theranostics: disease diagnostics and treatment using a single nanomaterial." Journal of Nanobiosensors in Disease Diagnosis (2015): 11-23. AbstractWebsite

Nanotheranostics takes advantage of nanotechnology-based systems in order to diagnose and treat a specific disease. This approach is particularly relevant for personalized medicine, allowing the detection of a disease at an early stage, to direct a suitable therapy toward the target tissue based on the molecular profile of the altered phenotype, subsequently facilitating disease monitoring and following treatment. A tailored strategy also enables to reduce the off-target effects associated with universal treatments and improve the safety profile of a given treatment. The unique optical properties of gold nanoparticles, their ease of surface modification, and high surface-to-volume ratio have made them central players in this area. By combining imaging, targeting, and therapeutic agents in a single vehicle, these nanoconjugates are (ought to be) an important tool in the clinics. In this review, the multifunctionality of gold nanoparticles as theranostics agents will be highlighted, as well as the requirements before the translation of these nanoplatforms into routine clinical practice.

Veigas, Bruno, Carla Portugal, Rita Valerio, Elvira Fortunato, Joao G. Crespo, and Pedro V. Baptista. "Scalable approach for the production of functional DNA based gold nanoprobes." Journal of Membrane Science 492 (2015): 528-535. Abstract

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Martins, Pedro, Mara Marques, Lidia Coito, Armando Pombeiro, Pedro V. Baptista, and Alexandra R. Fernandes. "Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions." ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY 9 (2015). AbstractWebsite

Over the past few years, modern medicinal chemistry has evolved towards providing us new and alternative chemotherapeutic compounds with high cytotoxicity towards tumor cells, alongside with reduced side effects in cancer patients. Organometallic compounds and their unique physic-chemical properties typically used in homogenous catalysis are now being translated as potential candidates for medical purposes. Their structural diversity, ligand exchange, redox and catalytic properties make them promising drug candidates for cancer therapy. Over the last decade this area has witnessed a steady growth and a few organometallic compounds have in fact already entered clinical trials, emphasizing its increasing importance and clinical relevance. Here we intend to stress out the different applications of organometallic compounds in medicine with emphasis on cancer therapy, as well as address setbacks regarding formulation issues, systemic toxicity and off-target effects. Advantages over classical coordination metal complexes, their nanovectorisation and specific molecular targets are also discussed.

Vinhas, R., C. Correia, P. Ribeiro, A. Lourenco, A. Sousa, A. Fernandes, and P. Baptista. "GOLD NANOPROBES IN THE DIAGNOSTIC OF CHRONIC MYELOID LEUKEMIA: DETECTION OF THE E14A2 BCR-ABL TRANSCRIPT DIRECTLY IN RNA SAMPLES." Leukemia Research 39 (2015): S90. Abstract

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Bernacka-Wojcik, Iwona, Hugo Aguas, Fabio Ferreira Carlos, Paulo Lopes, Pawel Jerzy Wojcik, Mafalda Nascimento Costa, Bruno Veigas, Rui Igreja, Elvira Fortunato, Pedro Viana Baptista, and Rodrigo Martins. "Single Nucleotide Polymorphism Detection Using Gold Nanoprobes and Bio-Microfluidic Platform With Embedded Micro lenses." Biotechnology and Bioengineering 112 (2015): 1210-1219. Abstract

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Conde, Joao, Furong Tian, Yulan Hernandez, Chenchen Bao, Pedro V. Baptista, Daxiang Cui, Tobias Stoeger, and Jesus M. de la Fuente. "RNAi-based glyconanoparticles trigger apoptotic pathways for in vitro and in vivo enhanced cancer-cell killing." Nanoscale 7 (2015): 9083-9091. Abstract

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McCully, Mark, Yulan Hernandez, Joao Conde, Pedro V. Baptista, Jesus M. de la Fuente, Andrew Hursthouse, David Stirling, and Catherine C. Berry. "Significance of the balance between intracellular glutathione and polyethylene glycol for successful release of small interfering RNA from gold nanoparticles." Nano Research 8 (2015): 3281-3292. Abstract

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Child, Hannah Winifred, Yulan Hernandez, João Conde, Margaret Mullin, Pedro V. Baptista, Jesus Maria de la Fuente, and Catherine C. Berry. "Gold nanoparticle-siRNA mediated oncogene knockdown at RNA and protein level, with associated gene effects." NANOMEDICINE 10 (2015): 2513-2525. AbstractWebsite

Aims: RNAi is a powerful tool for gene silencing that can be used to reduce undesirable overexpression of oncogenes as a novel form of cancer treatment. However, when using RNAi as a therapeutic tool there is potential for associated gene effects. This study aimed to utilize gold nanoparticles to deliver siRNA into HeLa cells. Results: Knockdown of the c-myc oncogene by RNAi, at the RNA, protein and cell proliferation level was achieved, while also identifying associated gene responses. Discussion: The gold nanoparticles used in this study present an excellent delivery platform for siRNA, but do note associated gene changes. Conclusion: The study highlights the need to more widely assess the cell physiological response to RNAi treatment, rather than focus on the immediate RNA levels.

Conde, João, Alfredo Ambrosone, Yulán Hernandez, Furong Tian, Mark McCully, Catherine C. Berry, Pedro V. Baptista, and Claudia T. " 15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics." NANO TODAY In Press (2015). Abstract

RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to down-regulate specific gene expression in diseased cells; opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the "do's and dont's" of the inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15.

Veigas, B., E. Fortunato, and P. V. Baptista. "Mobile based gold nanoprobe TB diagnostics for point-of-need." Methods in molecular biology (Clifton, N.J.) 1256 (2015): 41-56. Abstract

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Veigas, B., R. Branquinho, J. V. Pinto, P. J. Wojcik, R. Martins, E. Fortunato, and P. V. Baptista. "Ion sensing (EIS) real-time quantitative monitorization of isothermal DNA amplification." Biosens Bioelectron 52 (2014): 50-5. AbstractWebsite

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Bernacka-Wojcik, Iwona, Susana Ribeiro, Pawel Jerzy Wojcik, Pedro Urbano Alves, Tito Busani, Elvira Fortunato, Pedro Viana Baptista, José António Covas, Hugo Águas, Loic Hilliou, and Rodrigo Martins. " Experimental optimization of a passive planar rhombic micromixer with obstacles for effective mixing in a short channel length." RSC ADVANCES 4 (2014). AbstractWebsite

This paper presents the performance of a passive planar rhombic micromixer with diamond-shaped obstacles and a rectangular contraction between the rhombi. The device was experimentally optimized using water for high mixing efficiency and a low pressure drop over a wide range of Reynolds numbers (Re = 0.1–117.6) by varying geometrical parameters such as the number of rhombi, the distance between obstacles and the contraction width. Due to the large amount of data generated, statistical methods were used to facilitate and improve the results of the analysis. The results revealed a rank of factors influencing mixing efficiency: Reynolds number > number of rhombi > contraction width > inter-obstacles distance. The pressure drop measured after three rhombi depends mainly on Re and inter-obstacle distance. The resulting optimum geometry for the low Re regime has a contraction width of 101 μm and inter-obstacles distance of 93 μm, while for the high Re regime a contraction width of 400 μm and inter-obstacle distance of 121 μm are more appropriate. These mixers enabled 80% mixing efficiency creating a pressure drop of 6.0 Pa at Re = 0.1 and 5.1 × 104 Pa at Re = 117.6, with a mixer length of 2.5 mm. To the authors' knowledge, the developed mixer is one of the shortest planar passive micromixers reported to date.

Martins, Pedro, Daniela Rosa, Alexandra R. Fernandes, and Pedro V. Baptista. "Nanoparticle Drug Delivery Systems: Recent Patents and Applications in Nanomedicine." Recent Patents on Nanomedicine 3 (2014): 105-118. AbstractWebsite

Traditional methods of drug delivery present several drawbacks, mainly due to off-target effects that may originate severe side and toxic effect to healthy tissues. Parallel to the development of novel more effective drugs, particular effort has been dedicated to develop and optimize drug delivery vehicles capable of specifically targeting the required tissue/organ and to deliver the cargo only where and when it is needed. New drug delivery systems based on nanoscale devices showing new and improved pharmacokinetic and pharmacodynamics properties like enhanced bioavailability, high drug loading or systemic stability have surged in the past decade as promising solutions to the required therapeutic efficacy. Amongst these nanoscale vectors, nanoparticles for drug delivery, such as polymeric, lipidbased, ceramic or metallic nanoparticles, have been at the forefront of pharmaceutical development. The interest in nanomedicine for treatment and diagnosis is clearly reflected on the increasing number of publications and issued patents every year. Here, we provide a broad overview of novel nanoparticle based drug delivery systems, ranging from polymeric systems to metal nanoparticles, while simultaneously listing the most relevant related patents.

Baptista, Pedro Viana. "Gold nanobeacons: A potential nanotheranostics platform." Nanomedicine 9 (2014): 2247-50.Website
Restani, Rita B., João Conde, Pedro V. Baptista, Maria Teresa Cidade, Ana M. Bragança, Jorge Morgado, Ilídio J. Correia, Ana Aguiar-Ricardo, and Vasco D. B. Bonifacio. "Polyurea dendrimer for efficient cytosolic siRNA delivery." RSC ADVANCES 4 (2014): 54872. AbstractWebsite

The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are ‘smart’ biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.

Baptista, P. V. "Nanodiagnostics: leaving the research lab to enter the clinics?" Diagnosis (Berl) 1 (2014): 305-309. AbstractWebsite

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Larguinho, Miguel, Ana Cordeiro, Mario S. Diniz, Pedro M. Costa, and Pedro V. Baptista. "Metabolic and histopathological alterations in the marine bivalve Mytilus galloprovincialis induced by chronic exposure to acrylamide." Environmental Research 135 (2014): 55-62. Abstract

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Baptista, Pedro V. "Nanodiagnostics: leaving the research lab to enter the clinics?" Diagnosis 1 (2014): 305-309. AbstractWebsite

Nanotechnology has provided a plethora of valuable tools that can be applied for the detection of biomolecules and analytes relevant for diagnosis purposes – nanodiagnostics. This surging new field of molecular diagnostics has been revolutionizing laboratory procedures and providing new ways to assess disease biomarkers with increased sensitivity. While most of the reported nanodiagnostics systems are proof-of-concepts that demonstrate their efficacy in the lab, several nanodiagnostics platforms have already matured to a level that open the way for effective translation to the clinics. Nanodiagnostics platforms (e.g., gold nanoparticles containing systems) have been remarkably useful for the development of molecular diagnosis strategies for DNA/RNA detection and characterization, including systems suitable for point-of-care. How near are nanodiagnostics to go from the bench to the bedside?

Larguinho, Miguel, Daniela Correia, Mario S. Diniz, and Pedro V. Baptista. "Evidence of one-way flow bioaccumulation of gold nanoparticles across two trophic levels." Journal of Nanoparticle Research 16 (2014). Abstract

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Veigas, Bruno, Alexandra R. Fernandes, and Pedro V. Baptista. "AuNPs for identification of molecular signatures of resistance." Frontiers in Microbiology 5 (2014). Abstract

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Carlos, Fábio Ferreira, Orfeu Flores, Gonçalo Doria, and Pedro Viana Baptista. "Characterization of genomic SNP via colorimetric detection using a single gold nanoprobe." Analytical Biochemistry 465 (2014): 1-5. AbstractWebsite

Identification of specific nucleic acid sequences mediated by gold nanoparticles derivatized thiol-modified oligonucleotides (Au-nanoprobes) has been proven to be a useful tool in molecular diagnostics. Here, we demonstrate that, on optimization, detection may be simplified via the use of a single Au-nanoprobe to detect a single nucleotide polymorphism (SNP) in homo- or heterozygote condition. We validated this non-cross-linking approach through the analysis of 20 clinical samples using a single specific Au-nanoprobe for an SNP in the FTO (fat mass and obesity-associated) gene against direct DNA sequencing. Sensitivity, specificity, and limit of detection (LOD) were determined, and statistical differences were calculated by one-way analysis of variance (ANOVA) and a post hoc Tukey's test to ascertain whether there were any differences between Au-nanoprobe genotyped groups. For the first time, we show that the use of a single Au-nanoprobe can detect SNP for each genetic status (wild type, heterozygous, or mutant) with high degrees of sensitivity (87.50%) and specificity (91.67%).

Roma-Rodrigues, Catarina, Alexandra R. Fernandes, and Pedro Viana Baptista. "Exosome in Tumour Microenvironment: Overview of the Crosstalk between Normal and Cancer Cells." Biomed Research International (2014). Abstract

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