By Type: Journal Article

Nanoparticle Drug Delivery Systems: Recent Patents and Applications in Nanomedicine, Martins, Pedro, Rosa Daniela, Fernandes Alexandra R., and Baptista Pedro V. , Recent Patents on Nanomedicine, Volume 3, Issue 2, p.105-118, (2014) 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.

Experimental optimization of a passive planar rhombic micromixer with obstacles for effective mixing in a short channel length, Bernacka-Wojcik, Iwona, Ribeiro Susana, Wojcik Pawel Jerzy, Alves Pedro Urbano, Busani Tito, Fortunato Elvira, Baptista Pedro Viana, Covas José António, Águas Hugo, Hilliou Loic, and Martins Rodrigo , RSC ADVANCES, Volume 4, Issue 99, (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.

A low cost, safe, disposable, rapid and self-sustainable paper-based platform for diagnostic testing: lab-on-paper, Costa, M. N., Veigas B., Jacob J. M., Santos D. S., Gomes J., Baptista P. V., Martins R., Inacio J., and Fortunato E. , Nanotechnology, Volume 25, Number 9, (2014) Abstract

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Gold nanobeacons: A potential nanotheranostics platform, Baptista, Pedro Viana , Nanomedicine, Volume 9, Issue 15, p.2247-50, (2014) Website
Ion sensing (EIS) real-time quantitative monitorization of isothermal DNA amplification, Veigas, B., Branquinho R., Pinto J. V., Wojcik P. J., Martins R., Fortunato E., and Baptista P. V. , Biosens Bioelectron, Volume 52, p.50-5, (2014) AbstractWebsite

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

Polyurea dendrimer for efficient cytosolic siRNA delivery, Restani, Rita B., Conde João, Baptista Pedro V., Cidade Maria Teresa, Bragança Ana M., Morgado Jorge, Correia Ilídio J., Aguiar-Ricardo Ana, and Bonifacio Vasco D. B. , RSC ADVANCES, Volume 4, Issue 97, p.54872, (2014) 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.

Nanodiagnostics: leaving the research lab to enter the clinics?, Baptista, P. V. , Diagnosis (Berl), Volume 1, Number 4, p.305-309, (2014) AbstractWebsite

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Nanodiagnostics: leaving the research lab to enter the clinics?, Baptista, Pedro V. , Diagnosis, Volume 1, Issue 4, p.305–309, (2014) 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?

Gold nanoprobes for multi loci assessment of multi-drug resistant tuberculosis, Pedrosa, Pedro, Veigas Bruno, Machado Diana, Couto Isabel, Viveiros Miguel, and Baptista Pedro V. , Tuberculosis, Volume 94, Issue 3, p.332-337, (2014) AbstractWebsite

Tuberculosis, still one of the leading human infectious diseases, reported 8.7 million new cases in 2011 alone. Also, the increasing rate of multidrug-resistant tuberculosis (MDRTB) and its treatment difficulties pose a serious public health threat especially in developing countries. Resistance to isoniazid and rifampicin, first line antibiotics, is commonly associated with point mutations in katG, inhA and rpoB genes of Mycobacterium tuberculosis complex (MTBC). Therefore, the development of cheap, fast and simple molecular methods to assess susceptibility profiles would have a huge impact in the capacity of early diagnosis and treatment of MDRTB.

Gold nanoparticles functionalized with thiol-modified oligonucleotides (Au-nanoprobes) have shown the potential to provide a rapid and sensitive detection method for MTBC and single base mutations associated with antibiotic resistance, namely the characterization of the three most relevant codons in rpoB gene associated to rifampicin resistance. Here we extend the Au-nanoprobe approach towards discriminating specific mutations within inhA and rpoB genes in PCR amplified DNA from isolates. Using a multiplex PCR reaction for these two genes, it is possible to assess both loci in parallel, and extend the potential of the Au-nanoprobe method to MDRTB molecular characterization with special application in the most frequent Portuguese genotypes.

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

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Evidence of one-way flow bioaccumulation of gold nanoparticles across two trophic levels, Larguinho, Miguel, Correia Daniela, Diniz Mario S., and Baptista Pedro V. , Journal of Nanoparticle Research, Volume 16, Number 8, (2014) Abstract

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

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

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Fast Nucleotide identification using gold nanoparticle-based surface assisted laser desorption/ionisation, Larguinho, Miguel, Capelo José L., and Baptista Pedro V. , Talanta, Volume 105, p.417-421, (2013)
Gold-nanobeacons for simultaneous gene specific silencing and intracellular tracking of the silencing events, Conde, João, Rosa João, de la Fuente Jesús M., and Baptista Pedro V. , Biomaterials, Volume 34, p.2516-2523, (2013)
Isothermal DNA amplification coupled to Aunanoprobes for detection of mutations associated to Rifampicin resistance in Mycobacterium tuberculosis, Veigas, Bruno, Pedrosa Pedro, Couto Isabel, Viveiros Miguel, and Baptista Pedro V. , Journal of Nanobiotechnology, Volume 11, (2013) Abstract

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Bio-microfluidic platform for gold nanoprobe based DNA detection—application to Mycobacterium tuberculosis, Bernacka-Wojcik, Iwona, Lopes Paulo, Vaz Ana Catarina, Veigas Bruno, Wojcik Pawel Jerzy, Simões Pedro, Barata David, Fortunato Elvira, Baptista Pedro V., Águas Hugo, and Martins Rodrigo , Biosens Bioelectron, Volume 48, Issue 1, p.87-93, (2013) AbstractWebsite

We have projected and fabricated a microfluidic platform for DNA sensing that makes use of an optical colorimetric detection method based on gold nanoparticles. The platform was fabricated using replica moulding technology in PDMS patterned by high-aspect-ratio SU-8 moulds. Biochips of various geometries were tested and evaluated in order to find out the most efficient architecture, and the rational for design, microfabrication and detection performance is presented. The best biochip configuration has been successfully applied to the DNA detection of Mycobacterium tuberculosis using only 3 µl on DNA solution (i.e. 90 ng of target DNA), therefore a 20-fold reduction of reagents volume is obtained when compared with the actual state of the art.

Gold-Nanobeacons as a Theranostic System for the Detection and Inhibition of Specific Genes, Conde, João, Rosa João, and Baptista Pedro V. , Nature Protocol Exchange, (2013) AbstractWebsite

This protocol describes the synthesis and detailed calibration of a gold nanoparticle-based nanobeacon (Au-nanobeacon) as an innovative theranostic approach for detection and inhibition of sequence-specific DNA and RNA for in vitro and ex vivo applications. Under hairpin configuration, proximity to gold nanoparticles leads to fluorescence quenching; hybridization to a complementary target restores fluorescence emission due to the gold nanobeacons’ conformational reorganization that causes the fluorophore and the AuNP to part from each other. This concept can easily be extended and adapted to assist the in vitro evaluation of silencing potential of a given sequence to be later used for ex vivo gene silencing and RNAi approaches, with the ability to monitor real-time gene delivery action. The time range for the entire protocol is ~8 days, including synthesis, functionalization and calibration of Au-nanobeacons, RNAi and gene silencing assays.

Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an old idea?, Conde, Joao, de la Fuente Jesus M., and V. Baptista Pedro , Frontiers in Pharmacology, Volume 4, (2013) Abstract

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Plastic Compatible Sputtered Ta2O5 Sensitive Layer for Oxide Semiconductor TFT Sensors, Branquinho, R., Pinto J. V., Busani T., Barquinha P., Pereira L., Baptista P. V., Martins R., and Fortunato E. , J. Display Technol, Volume 9, p.723-728, (2013)
THE CHEMISTRY AND BIOLOGY OF GOLD NANOPARTICLE-MEDIATED PHOTOTHERMAL THERAPY: PROMISES AND CHALLENGES, Cabral, Rita, and Baptista Pedro V. , Nano Life, Volume 3, Issue 3, p.330001, (2013) AbstractWebsite

Under laser radiation, cells labeled with gold nanoparticles (AuNPs) are believed to suffer thermal damage due to the transfer of the absorbed light from the AuNPs to the cells. This process, which involves complex mechanisms such as the rapid electron–phonon decay in the AuNPs, followed by phonon–phonon relaxation, culminates in the localized heating of both the AuNPs and the cells, setting the rational for the use of these nanostructures, under laser light, in cancer photothermal therapy (PTT). Here, we discuss the chemical and biological aspects of this promising new therapeutic approach, including the advantages over conventional cancer therapies and the challenges that scientists still need to overcome to progress toward translation research

Coupling an universal primer to SBE combined spectral codification strategy for single nucleotide polymorphism analysis., Cordeiro, M., Giestas L., Lima J. C., and Baptista Pedro Viana , J Biotechnol, Volume 168, Issue 1, p.90-94, (2013) AbstractWebsite

We previously reported a strategy that combines Förster resonance energy transfer (FRET) based spectral codification with a single base extension (SBE) reaction for single nucleotide sequence discrimination in solution. This strategy is capable of unequivocally detect the allele variants present in solution. To extend the use of this tool to any locus of interest, it would be required the development of an universal approach capable of combining a sequence specific SBE primer to an universal sequence labeled and optimized for spectral codification.
Here, we extend this concept to a general strategy by means of a labeled universal oligonucleotide primer (donor), a sequence specific primer that allows for incorporation of the complementary acceptor labeled ddNTP, which allows discrimination the allele variant in the sample via the unambiguous FRET signature of the donor/acceptor pair.

Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an old idea?, Conde, João, de la Fuente Jesus M., and Baptista Pedro V. , Front. Pharmacol., (2013)
In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models, Conde, Joao, Tian Furong, Hernandez Yulan, Bao Chenchen, Cui Daxiang, Janssen Klaus-Peter, Ricardo Ibarra M., Baptista Pedro V., Stoeger Tobias, and de la Fuente Jesus M. , Biomaterials, Volume 34, Number 31, p.7744-7753, (2013) Abstract

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