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Baptista, Pedro V., Matthew P. McCusker, Andreia Carvalho, Daniela A. Ferreira, Niamh M. Mohan, Marta Martins, and Alexandra R. Fernandes. "Nano-Strategies to Fight Multidrug Resistant Bacteria—“A Battle of the Titans”." Frontiers in Microbiology 9 (2018): 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.

Veigas, Bruno, Gonçalo Doria, and Pedro V. Baptista. "Nanodiagnostics for tuberculosis." In Understanding Tuberculosis - Global Experiences and Innovative Approaches to the Diagnosis, edited by Pere-Joan Cardona. InTech, 2011.
Doria, Gonçalo, Ricardo Franco, and Pedro Baptista. "Nanodiagnostics: Fast Colorimetric Method for Single Nucleotide Polymorphism/Mutation Detection." IET Nanobiotechnol. 1 (2007): 53-57.
Doria, G., R. Franco, and P. Baptista. "Nanodiagnostics: fast colorimetric method for single nucleotide polymorphism/mutation detection." Iet Nanobiotechnology 1 (2007): 53-57. 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?

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

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Conde, João, Jesus M. de la Fuente, and Pedro V. Baptista. "Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an old idea?" Front. Pharmacol. (2013).
Conde, J., J. M. de la Fuente, and P. V. Baptista. "Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an old idea?" Front Pharmacol 4 (2013): 134. AbstractWebsite

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

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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.

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

McCully, Mark, Joao Conde, Pedro V. Baptista, Margaret Mullin, Matthew J. Dalby, and Catherine C. Berry. "Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells." Plos One 13 (2018). Abstract

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Larguinho, Miguel, Sara Figueiredo, Ana Cordeiro, Fábio Ferreira Carlos, Milton Cordeiro, Pedro Pedrosa, and Pedro Viana Baptista. "Nanoparticles for Diagnostics and Imaging." In Frontiers in Nanomedicine, edited by Maria Luisa Bondì Bondì, Chiara Botto and Erika Amore, 3-46. Bentham Science, 2015. Abstractsample.pdf

Nanoparticles possess unique optical and physic-chemical properties that may potentiate applications in biomedicine, in particular in diagnostics, therapy and imaging. Advances on biomolecular diagnostics strategies have greatly focused on single molecule detection and characterization of DNA, RNA or proteins through improved nanoparticle-based platforms. Nanoparticles improve analytical capability when compared to traditional techniques with high resolution and medium-high throughput. Also, particular interest has been directed at SNP detection, gene expression profiles and biomarker characterization through colorimetric, spectrometric or electrochemical strategies.
Molecular imaging has also benefited from the introduction of nanoparticles in standard techniques towards non-invasive imaging procedures that can be used to highlight regions of interest, allowing the characterization of biological processes at the cellular and/or molecular level. Several imaging modalities are associated with low sensitivity, an issue that can be tackled by the use of probes, e.g. contrast agents for X-ray and magnetic resonance imaging, radiolabelled molecules for nuclear medicine. Furthermore, nanoparticles can be used as vehicles that deliver specifically these contrast agents, leading to overcome the limitations of conventional modalities.
This chapter will discuss the use of nanoparticles in biomolecular recognition and imaging applications, focusing those already being translated into clinical settings. Current knowledge will be addressed as well as its evolution towards the future of nanoparticle-based biomedical applications.

Baptista, P. V., G. Doria, P. Quaresma, M. Cavadas, C. S. Neves, I. Gomes, P. Eaton, E. Pereira, and R. Franco. "Nanoparticles in molecular diagnostics." Prog. Mol. Biol. Transl. Sci. 104 (2011): 427-488.
Baptista, P. V., G. Doria, P. Quaresma, M. Cavadas, C. S. Neves, I. Gomes, P. Eaton, E. Pereira, and R. Franco. "Nanoparticles in molecular diagnostics." Prog Mol Biol Transl Sci 104 (2011): 427-88. AbstractWebsite

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Baptista, Pedro V., Goncalo Doria, Pedro Quaresma, Miguel Cavadas, Cristina S. Neves, Ines Gomes, Peter Eaton, Eulalia Pereira, Ricardo Franco, and A. Villaverde. "Nanoparticles in Molecular Diagnostics." Nanoparticles in Translational Science and Medicine 104 (2011): 427-488. Abstract

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Baptista, Pedro V., Gonçalo Doria, Pedro Quaresma, Miguel Cavadas, Cristina S. Neves, Inês Gomes, Peter Eaton, Eulália Pereira, and Ricardo Franco. "Nanoparticles in molecular diagnostics. Nanoparticles in Translational Science and Medicine." In Progress in Molecular Biology and Translational Science, edited by A. Villaverde and Michael P. Conn. Elsevier, 2012.
Vinhas, Raquel, Rita Mendes, Alexandra R. Fernandes, and Pedro V. Baptista. "Nanoparticles-Emerging Potential for Managing Leukemia and Lymphoma." Frontiers in Bioengineering and Biotechnology 5 (2017). Abstract

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Vinhas, Raquel, Rita Mendes, Alexandra R. Fernandes, and Pedro V. Baptista. "Nanoparticles—Emerging Potential for Managing Leukemia and Lymphoma." Front. Bioeng. Biotechnol 5 (2017): 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.

Conde, João, João Rosa, João C. Lima, and Pedro V. Baptista. "Nanophotonics for Molecular Diagnostics and Therapy Applications." Int. J. Photoenergy 619530 (2012).
Conde, J., J. Rosa, J. C. Lima, and P. V. Baptista. "Nanophotonics for Molecular Diagnostics and Therapy Applications." International Journal of Photoenergy (2012). Abstract

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Fernandes, Alexandra R., and Pedro Viana Baptista. "Nanotechnology for Cancer Diagnostics and Therapy – An Update on Novel Molecular Players." Current Cancer Therapy Reviews 9 (2013): 164-172. AbstractWebsite

Nanotechnology has emerged as a "disruptive technology" that may provide researchers with new and innovative ways to diagnose, treat and monitor cancer. In fact, nanomedicine approaches have delivered several strategies, such as new imaging agents, real-time assessments of therapeutic and surgical efficacy, multifunctional, targeted devices capable of bypassing biological barriers to target and silence specific pathways in tumours. Of particular interest, has been the increased capability to deliver multiple therapeutic agents directly to bulk cancer cells and cancer stem cells that play a critical role in cancer growth and metastasis. These multifunctional targeted nanoconjugates are also capable of avoiding cancer resistance and monitor predictive molecular changes that open the path for preventive action against pre-cancerous cells, minimizing costs and incidence of relapses. A myriad of nanoconjugates with effective silencing and site-targeting moieties can be developed by incorporating a diverse selection of targeting, diagnostic, and therapeutic components. A discussion of the integrative effort of nanotechnology systems with recent developments of biomolecular interactions in cancer progression is clearly required. Here, we will update the state of the art related to the development and applications of nanoscale platforms and novel biomolecular players in cancer diagnosis, imaging and treatment.

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

Neves, C. S., P. Quaresma, P. V. Baptista, P. A. Carvalho, JP Araujo, E. Pereira, and P. Eaton. "New insights into the use of magnetic force microscopy to discriminate between magnetic and nonmagnetic nanoparticles." Nanotechnology 21 (2010). Abstract

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Conde, Joao, Goncalo Doria, and Pedro Baptista. "Noble metal nanoparticles applications in cancer." Journal of drug delivery 2012 (2012): 751075. Abstract

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