Publications in the Year: 2017

Journal Article

Carlos, FF, Veigas B, Matias AS, Doria G, Flores O, Baptista PV.  2017.  Allele specific LAMP- gold nanoparticle for characterization of single nucleotide polymorphisms. Biotechnol Rep (Amst). 16:21-25. AbstractWebsite

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Mendes, R, Pedrosa P, Lima JC, Fernandes AR, Baptista PV.  2017.  Photothermal enhancement of chemotherapy in breast cancer by visible irradiation of Gold Nanoparticles. Scientific Reports. 7 Abstract

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Veigas, B, Pinto J, Vinhas R, Calmeiro T, Martins R, Fortunato E, Baptista PV.  2017.  Quantitative real-time monitoring of RCA amplification of cancer biomarkers mediated by a flexible ion sensitive platform. Biosensors & Bioelectronics. 91:788-795. Abstract

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Vinhas, R, Mendes R, Fernandes AR, Baptista PV.  2017.  Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma, 2017. Front. Bioeng. Biotechnol. 5:79. AbstractWebsite

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, nanoparticles enhance the therapeutic efficacy of anticancer agents when compared to conventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine’s accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, nanoparticles have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from pre-clinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by nanoparticles in this combined strategy.

Fernandes, AR, Jesus J, Martins P, Figueiredo S, Rosa D, Martins LMRDRS, Corvo ML, Carvalheiro MC, Costa PM, Baptista PV.  2017.  Multifunctional gold-nanoparticles: A nanovectorization tool for the targeted delivery of novel chemotherapeutic agents. Journal of Controlled Release. 245:52-61. Abstract

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Roma-Rodrigues, C, Pereira F, Alves de Matos AP, Fernandes M, Baptista PV, Fernandes AR.  2017.  Smuggling gold nanoparticles across cell types - A new role for exosomes in gene silencing. Nanomedicine-Nanotechnology Biology and Medicine. 13:1389-1398., Number 4 Abstract

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Vinhas, R, Fernandes A, Baptista PV.  2017.  Gold Nanoparticles for BCR-ABL1 Gene Silencing: Improving Tyrosine Kinase Inhibitor Efficacy in Chronic Myeloid Leukemia. Molecular Therapy Nucleic Acids. 7:408-416. AbstractWebsite

Introduction of tyrosine kinase inhibitors for chronic myeloid leukemia treatment is associated with a 63% probability of maintaining a complete cytogenetic response, meaning that over 30% patients require an alternative methodology to overcome resistance, tolerance, or side effects. Considering the potential of nanotechnology in cancer treatment and the benefits of a combined therapy with imatinib, a nanoconjugate was designed to achieve BCR-ABL1 gene silencing. Gold nanoparticles were functionalized with a single-stranded DNA oligonucleotide that selectively targets the e14a2 BCR-ABL1 transcript expressed by K562 cells. This gold (Au)-nanoconjugate showed great efficacy in gene silencing that induced a significant increase in cell death. Variation of BCL-2 and BAX protein expression, an increase of caspase-3 activity, and apoptotic bodies in cells treated with the nanoconjugate demonstrate its aptitude for inducing apoptosis on K562 BCR-ABL1-expressing cells. Moreover, the combination of the silencing Au-nanoconjugate with imatinib prompted a decrease of imatinib IC50. This Au-nanoconjugate was also capable of inducing the loss of viability of imatinib-resistant K562 cells. This strategy shows that combination of Au-nanoconjugate and imatinib make K562 cells more vulnerable to chemotherapy and that the Au-nanoconjugate alone may overcome imatinib-resistance mechanisms, thus providing an effective treatment for chronic myeloid leukemia patients who exhibit drug tolerance.

Fernandes, AR, Baptista PV.  2017.  Gene Silencing Using Multifunctionalized Gold Nanoparticles for Cancer Therapy.. Methods in molecular biology (Clifton, N.J.). 1530:319-336. Abstract

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Raposo, LR, Roma-Rodrigues C, Jesus J, Martins LMDRS, Pombeiro AJ, Baptista PV, Fernandes AR.  2017.  Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds. Veterinary and Comparative Oncology. 15:1537-1542., Number 4 Abstract

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Mendes, R, Fernandes AR, Baptista PV.  2017.  Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery? Genes. 3(8):94. AbstractWebsite

Gene therapy arises as a great promise for cancer therapeutics due to its potential to silence genes involved in tumor development. In fact, there are some pivotal gene drivers that suffer critical alterations leading to cell transformation and ultimately to tumor growth. In this vein, gene silencing has been proposed as an active tool to selectively silence these molecular triggers of cancer, thus improving treatment. However, naked nucleic acid (DNA/RNA) sequences are reported to have a short lifetime in the body, promptly degraded by circulating enzymes, which in turn speed up elimination and decrease the therapeutic potential of these drugs. The use of nanoparticles for the effective delivery of these silencers to the specific target locations has allowed researchers to overcome this issue. Particularly, gold nanoparticles (AuNPs) have been used as attractive vehicles for the target-specific delivery of gene-silencing moieties, alone or in combination with other drugs. We shall discuss current trends in AuNP-based delivery of gene-silencing tools, considering the promising road ahead without overlooking existing concerns for their translation to clinics

Coelho, B, Veigas B, Fortunato E, Martins R, Aguas H, Igreja R, Baptista PV.  2017.  Digital Microfluidics for Nucleic Acid Amplification. Sensors. 17, Number 7 Abstract

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Raposo, LR, Roma-Rodrigues C, Faisca P, Alves M, Henriques J, Carvalheiro MC, Corvo ML, Baptista PV, Pombeiro AJ, Fernandes AR.  2017.  Immortalization and characterization of a new canine mammary tumour cell line FR37-CMT. Veterinary and Comparative Oncology. 15:952-967., Number 3 Abstract

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Cordeiro, M, Carvalho L, Silva J, Saúde L, Fernandes AR, Baptista. PV.  2017.  Gold nanobeacons for tracking gene silencing in Zebrafish. Nanomaterials. AbstractWebsite

The use of gold nanoparticles for effective gene silencing has demonstrated its potential as a tool for gene expression experiments and for the treatment of several diseases. Here, we used a gold nanobeacon designed to specifically silence the enhanced green fluorescence protein (EGFP) mRNA in embryos of a fli-EGFP transgenic zebrafish line, while simultaneously allowing the tracking and localization of the silencing events via the beacon’s emission. Fluorescence imaging measurements demonstrated a decrease of the EGFP emission with a concomitant increase in the fluorescence of the Au-nanobeacon. Furthermore, microinjection of the Au-nanobeacon led to a negligible difference in mortality and malformations in comparison to the free oligonucleotide, indicating that this system is a biocompatible platform for the administration of gene silencing moieties. Together, these data illustrate the potential of Au-nanobeacons as tools for in vivo zebrafish gene modulation with low toxicity which may be used towards any gene of interest.

Coelho, BJ, Veigas B, Aguas H, Fortunato E, Martins R, Baptista PV, Igreja R.  2017.  A Digital Microfluidics Platform for Loop-Mediated Isothermal Amplification Detection. Sensors. 17, Number 11 Abstract

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Pedrosa, P, Heuer-Jungemann A, Kanaras AG, Fernandes AR, Baptista PV.  2017.  Potentiating angiogenesis arrest in vivo via laser irradiation of peptide functionalised gold nanoparticles. Journal of Nanobiotechnology. 15 Abstract

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Roma-Rodrigues, C, Raposo L, Cabral R, Paradinha F, Baptista PV, Fernandes AR.  2017.  Tumor microenvironment modulation via gold nanoparticles targeting malicious exosomes: implications in cancer diagnostics and Therapy. Int. J. Mol. Sci.. 18(1):162. AbstractWebsite

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

Vinhas, R, Mendes R, Fernandes AR, Baptista PV.  2017.  Nanoparticles-Emerging Potential for Managing Leukemia and Lymphoma. Frontiers in Bioengineering and Biotechnology. 5 Abstract

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