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Dr. Maria Manuela Gaspar
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Portugal

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Research Keywords & Expertise

0 Liposomes
0 Melanoma
0 Pancreatic Cancer
0 Tuberculosis
0 leishmaniasis

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Liposomes
Melanoma
drug delivery systems
Tuberculosis
Colon cancer
Pancreatic Cancer
leishmaniasis
Lipid-based systems
Bacterial Infections
In vitro screening of new compounds

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Short Biography

Design, development and biological evaluation of drug delivery systems for improving the therapeutic index of incorporated molecules in infectious, inflammatory and cancer animal models. Establishment of methodologies for assessing the in vitro and in vivo profile of nanoformulations.

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Journal article
Published: 18 May 2021 in International Journal of Molecular Sciences
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Parkinson’s disease (PD) is the second most common neurodegenerative disorder, mainly characterized by motor deficits correlated with progressive dopaminergic neuronal loss in the substantia nigra pars compacta (SN). Necroptosis is a caspase-independent form of regulated cell death mediated by the concerted action of receptor-interacting protein 3 (RIP3) and the pseudokinase mixed lineage domain-like protein (MLKL). It is also usually dependent on RIP1 kinase activity, influenced by further cellular clues. Importantly, necroptosis appears to be strongly linked to several neurodegenerative diseases, including PD. Here, we aimed at identifying novel chemical inhibitors of necroptosis in a PD-mimicking model, by conducting a two-step screening. Firstly, we phenotypically screened a library of 31 small molecules using a cellular model of necroptosis and, thereafter, the hit compound effect was validated in vivo in a sub-acute 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) PD-related mouse model. From the initial compounds, we identified one hit—Oxa12—that strongly inhibited necroptosis induced by the pan-caspase inhibitor zVAD-fmk in the BV2 murine microglia cell line. More importantly, mice exposed to MPTP and further treated with Oxa12 showed protection against MPTP-induced dopaminergic neuronal loss in the SN and striatum. In conclusion, we identified Oxa12 as a hit compound that represents a new chemotype to tackle necroptosis. Oxa12 displays in vivo effects, making this compound a drug candidate for further optimization to attenuate PD pathogenesis.

ACS Style

Sara Oliveira; Pedro Dionísio; Maria Gaspar; Maria Ferreira; Catarina Rodrigues; Rita Pereira; Mónica Estevão; Maria Perry; Rui Moreira; Carlos Afonso; Joana Amaral; Cecília Rodrigues. Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice. International Journal of Molecular Sciences 2021, 22, 5289 .

AMA Style

Sara Oliveira, Pedro Dionísio, Maria Gaspar, Maria Ferreira, Catarina Rodrigues, Rita Pereira, Mónica Estevão, Maria Perry, Rui Moreira, Carlos Afonso, Joana Amaral, Cecília Rodrigues. Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice. International Journal of Molecular Sciences. 2021; 22 (10):5289.

Chicago/Turabian Style

Sara Oliveira; Pedro Dionísio; Maria Gaspar; Maria Ferreira; Catarina Rodrigues; Rita Pereira; Mónica Estevão; Maria Perry; Rui Moreira; Carlos Afonso; Joana Amaral; Cecília Rodrigues. 2021. "Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice." International Journal of Molecular Sciences 22, no. 10: 5289.

Journal article
Published: 15 May 2021 in Pharmaceuticals
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Sambucus nigra L. (S. nigra) is a shrub widespread in Europe and western Asia, traditionally used in medicine, that has become popular in recent years as a potential source of a wide range of interesting bioactive compounds. The aim of the present work was to develop a topical S. nigra extract formulation based on ethosomes and thus to support its health claims with scientific evidence. S. nigra extract was prepared by an ultrasound-assisted method and then included in ethosomes. The ethosomes were analyzed in terms of their size, stability over time, morphology, entrapment capacity (EC), extract release profile, stability over time and several biological activities. The prepared ethosomes were indicated to be well defined, presenting sizes around 600 nm. The extract entrapment capacity in ethosomes was 73.9 ± 24.8%, with an interesting slow extract release profile over 24 h. The extract-loaded ethosomes presented collagenase inhibition activity and a very good skin compatibility after human application. This study demonstrates the potential use of S. nigra extract incorporated in ethosomes as a potential cosmeceutical ingredient and on further studies should be performed to better understand the impact of S. nigra compounds on skin care over the time.

ACS Style

Ana Mota; Inês Prazeres; Henrique Mestre; Andreia Bento-Silva; Maria Rodrigues; Noélia Duarte; Ana Serra; Maria Bronze; Patrícia Rijo; Maria Gaspar; Ana Viana; Lia Ascensão; Pedro Pinto; Pradeep Kumar; António Almeida; Catarina Reis. A Newfangled Collagenase Inhibitor Topical Formulation Based on Ethosomes with Sambucus nigra L. Extract. Pharmaceuticals 2021, 14, 467 .

AMA Style

Ana Mota, Inês Prazeres, Henrique Mestre, Andreia Bento-Silva, Maria Rodrigues, Noélia Duarte, Ana Serra, Maria Bronze, Patrícia Rijo, Maria Gaspar, Ana Viana, Lia Ascensão, Pedro Pinto, Pradeep Kumar, António Almeida, Catarina Reis. A Newfangled Collagenase Inhibitor Topical Formulation Based on Ethosomes with Sambucus nigra L. Extract. Pharmaceuticals. 2021; 14 (5):467.

Chicago/Turabian Style

Ana Mota; Inês Prazeres; Henrique Mestre; Andreia Bento-Silva; Maria Rodrigues; Noélia Duarte; Ana Serra; Maria Bronze; Patrícia Rijo; Maria Gaspar; Ana Viana; Lia Ascensão; Pedro Pinto; Pradeep Kumar; António Almeida; Catarina Reis. 2021. "A Newfangled Collagenase Inhibitor Topical Formulation Based on Ethosomes with Sambucus nigra L. Extract." Pharmaceuticals 14, no. 5: 467.

Journal article
Published: 15 April 2021 in International Journal of Molecular Sciences
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Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

ACS Style

Maria Quitério; Sandra Simões; Andreia Ascenso; Manuela Carvalheiro; Ana Leandro; Isabel Correia; Ana Viana; Pedro Faísca; Lia Ascensão; Jesús Molpeceres; Maria Gaspar; Catarina Reis. Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach. International Journal of Molecular Sciences 2021, 22, 4087 .

AMA Style

Maria Quitério, Sandra Simões, Andreia Ascenso, Manuela Carvalheiro, Ana Leandro, Isabel Correia, Ana Viana, Pedro Faísca, Lia Ascensão, Jesús Molpeceres, Maria Gaspar, Catarina Reis. Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach. International Journal of Molecular Sciences. 2021; 22 (8):4087.

Chicago/Turabian Style

Maria Quitério; Sandra Simões; Andreia Ascenso; Manuela Carvalheiro; Ana Leandro; Isabel Correia; Ana Viana; Pedro Faísca; Lia Ascensão; Jesús Molpeceres; Maria Gaspar; Catarina Reis. 2021. "Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach." International Journal of Molecular Sciences 22, no. 8: 4087.

Review
Published: 02 April 2021 in Molecules
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Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

ACS Style

Magda Ferreira; Maria Ogren; Joana Dias; Marta Silva; Solange Gil; Luís Tavares; Frederico Aires-Da-Silva; Maria Gaspar; Sandra Aguiar. Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance. Molecules 2021, 26, 2047 .

AMA Style

Magda Ferreira, Maria Ogren, Joana Dias, Marta Silva, Solange Gil, Luís Tavares, Frederico Aires-Da-Silva, Maria Gaspar, Sandra Aguiar. Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance. Molecules. 2021; 26 (7):2047.

Chicago/Turabian Style

Magda Ferreira; Maria Ogren; Joana Dias; Marta Silva; Solange Gil; Luís Tavares; Frederico Aires-Da-Silva; Maria Gaspar; Sandra Aguiar. 2021. "Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance." Molecules 26, no. 7: 2047.

Journal article
Published: 30 March 2021 in Biomolecules
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The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.

ACS Style

Joana Lopes; Tânia Ferreira-Gonçalves; Isabel Figueiredo; Cecília Rodrigues; Hugo Ferreira; David Ferreira; Ana Viana; Pedro Faísca; Maria Gaspar; João Coelho; Catarina Silva; Catarina Reis. Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma. Biomolecules 2021, 11, 511 .

AMA Style

Joana Lopes, Tânia Ferreira-Gonçalves, Isabel Figueiredo, Cecília Rodrigues, Hugo Ferreira, David Ferreira, Ana Viana, Pedro Faísca, Maria Gaspar, João Coelho, Catarina Silva, Catarina Reis. Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma. Biomolecules. 2021; 11 (4):511.

Chicago/Turabian Style

Joana Lopes; Tânia Ferreira-Gonçalves; Isabel Figueiredo; Cecília Rodrigues; Hugo Ferreira; David Ferreira; Ana Viana; Pedro Faísca; Maria Gaspar; João Coelho; Catarina Silva; Catarina Reis. 2021. "Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma." Biomolecules 11, no. 4: 511.

Journal article
Published: 12 March 2021 in Cancers
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Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues’ temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC’s specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future.

ACS Style

Mariana Amaral; Adília Charmier; Ricardo Afonso; José Catarino; Pedro Faísca; Lina Carvalho; Lia Ascensão; João Coelho; M. Gaspar; Catarina Reis. Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward. Cancers 2021, 13, 1242 .

AMA Style

Mariana Amaral, Adília Charmier, Ricardo Afonso, José Catarino, Pedro Faísca, Lina Carvalho, Lia Ascensão, João Coelho, M. Gaspar, Catarina Reis. Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward. Cancers. 2021; 13 (6):1242.

Chicago/Turabian Style

Mariana Amaral; Adília Charmier; Ricardo Afonso; José Catarino; Pedro Faísca; Lina Carvalho; Lia Ascensão; João Coelho; M. Gaspar; Catarina Reis. 2021. "Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward." Cancers 13, no. 6: 1242.

Journal article
Published: 09 March 2021 in International Journal of Pharmaceutics
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Colorectal carcinoma is a complex malignancy and current therapies are hampered by systemic toxicity and tumor resistance to treatment. In the field of cancer therapy, copper (Cu) compounds hold great promise, with some reaching clinical trials. However, the anticancer potential of Cu complexes has not yet been fully disclosed due to speciation in biological systems, leading to inactivation and/or potential side effects. This is the case of the widely studied Cu(II) complexes featuring phenanthroline ligands, with potent antiproliferative effects in vitro, but often failing in vivo. Aiming to overcome these limitations and maximize its anticancer effects in vivo, the Cu(II) complex (Cu(1,10-phenanthroline)Cl2) (Cuphen), displaying IC50 values <6 μM against different tumor cell lines, was loaded in long circulating liposomes with pH-sensitive properties (F1, DMPC:CHEMS:DSPE-PEG; F2, DOPE:CHEMS:DMPC:DSPE-PEG). This enabled a pH-dependent Cuphen release, with F1 and F2 releasing 36/78% and 47/94% of Cuphen at pH 6/4.5, respectively. The so formed nanoformulations preserved Cuphen effects towards cancer cell lines, with F2 presenting IC50 of 2.7 μM and 4.9 μM towards colon cancer CT-26 and HCT-116 cells, respectively. Additional in vitro studies confirmed that Cuphen antiproliferative activity towards colon cancer cells does not rely on cell cycle effect. Furthermore, in these cells, Cuphen reduced glycerol permeation and impaired cell migration. At 24 h incubation, wound closure was reduced by Cuphen, with migration values of 29% vs 54% (control) and 45% (1,10-phenanthroline) in CT-26 cells, and 33% vs ~44% (control and 1,10-phenanthroline) in HCT-116 cells. These effects were probably due to inhibition of aquaglyceroporins, membrane water and glycerol channels that are often abnormally expressed in tumors. In a syngeneic murine colon cancer model, F2 significantly reduced tumor progression, compared to the control group and to mice treated with free Cuphen or with the ligand, 1,10-phenanthroline, without eliciting toxic side effects. F2 led to a tumor volume reduction of ca. 50%. This was confirmed by RTV analysis, where F2 reached a value of 1.3 vs 4.4 (Control), 5.8 (Phen) and 3.8 (free Cuphen). These results clearly demonstrated the important role of the Cu(II) for the observed biological activity that was maximized following the association to a lipid-based nanosystem. Overall, this study represents a step forward in the development of pH-sensitive nanotherapeutic strategies of metallodrugs for colon cancer management.

ACS Style

Jacinta O. Pinho; Inês V. da Silva; Joana D. Amaral; Cecília M.P. Rodrigues; Angela Casini; Graça Soveral; M. Manuela Gaspar. Therapeutic potential of a copper complex loaded in pH-sensitive long circulating liposomes for colon cancer management. International Journal of Pharmaceutics 2021, 599, 120463 .

AMA Style

Jacinta O. Pinho, Inês V. da Silva, Joana D. Amaral, Cecília M.P. Rodrigues, Angela Casini, Graça Soveral, M. Manuela Gaspar. Therapeutic potential of a copper complex loaded in pH-sensitive long circulating liposomes for colon cancer management. International Journal of Pharmaceutics. 2021; 599 ():120463.

Chicago/Turabian Style

Jacinta O. Pinho; Inês V. da Silva; Joana D. Amaral; Cecília M.P. Rodrigues; Angela Casini; Graça Soveral; M. Manuela Gaspar. 2021. "Therapeutic potential of a copper complex loaded in pH-sensitive long circulating liposomes for colon cancer management." International Journal of Pharmaceutics 599, no. : 120463.

Journal article
Published: 02 March 2021 in Sustainable Chemistry
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The task-specific design of ionic liquids (ILs) has emerged in several industrial and pharmaceutical applications. The family of ILs with fluorine tags equal to or longer than four carbon atoms, the fluorinated ionic liquids (FILs), combine the best properties of ILs with the ones of perfluorinated compounds, and are being designed for several specific purposes. In the pharmaceutical field, there is an urgency to search for novel antibacterial agents to overcome problems associated to antimicrobial resistances. Then, the main purpose of this work is to evaluate the environmental impact and the ability of FILs to be used as antibacterial agents against Pseudomonas stutzeri bacteria. Beyond its rare pathogenicity, these bacteria are also used as a bioremediation agent to treat several contamination sites. Then, it is important to determine which FILs have antibacterial properties, and which do not impact the bacterial growth. The biocompatibility of FILs was also evaluated through their hemolytic activity and represent a step forward the application of FILs in pharmaceutical applications. The results proved that high concentrations of FILs can have a reduced ecotoxicity and a high biocompatibility. [C8C1Im][CF3SO3] was identified as the most promising compound to be used as an antibacterial agent since it prevents the growth of bacteria at concentrations compatible with the red blood cells’ viability.

ACS Style

Nicole Vieira; Ana Oliveira; João Araújo; Maria Gaspar; Ana Pereiro. Ecotoxicity and Hemolytic Activity of Fluorinated Ionic Liquids. Sustainable Chemistry 2021, 2, 115 -126.

AMA Style

Nicole Vieira, Ana Oliveira, João Araújo, Maria Gaspar, Ana Pereiro. Ecotoxicity and Hemolytic Activity of Fluorinated Ionic Liquids. Sustainable Chemistry. 2021; 2 (1):115-126.

Chicago/Turabian Style

Nicole Vieira; Ana Oliveira; João Araújo; Maria Gaspar; Ana Pereiro. 2021. "Ecotoxicity and Hemolytic Activity of Fluorinated Ionic Liquids." Sustainable Chemistry 2, no. 1: 115-126.

Journal article
Published: 02 March 2021 in Pharmaceutics
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Staphylococcus aureus biofilm-associated infections are a major public health concern. Current therapies are hampered by reduced penetration of antibiotics through biofilm and low accumulation levels at infected sites, requiring prolonged usage. To overcome these, repurposing antibiotics in combination with nanotechnological platforms is one of the most appealing fast-track and cost-effective approaches. In the present work, we assessed the potential therapeutic benefit of three antibiotics, vancomycin, levofloxacin and rifabutin (RFB), through their incorporation in liposomes. Free RFB displayed the utmost antibacterial effect with MIC and MBIC50 below 0.006 µg/mL towards a methicillin susceptible S. aureus (MSSA). RFB was selected for further in vitro studies and the influence of different lipid compositions on bacterial biofilm interactions was evaluated. Although positively charged RFB liposomes displayed the highest interaction with MSSA biofilms, RFB incorporated in negatively charged liposomes displayed lower MBIC50 values in comparison to the antibiotic in the free form. Preliminary safety assessment on all RFB formulations towards osteoblast and fibroblast cell lines demonstrated that a reduction on cell viability was only observed for the positively charged liposomes. Overall, negatively charged RFB liposomes are a promising approach against biofilm S. aureus infections and further in vivo studies should be performed.

ACS Style

Magda Ferreira; Sandra Pinto; Frederico Aires-Da-Silva; Ana Bettencourt; Sandra Aguiar; Maria Gaspar. Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms. Pharmaceutics 2021, 13, 321 .

AMA Style

Magda Ferreira, Sandra Pinto, Frederico Aires-Da-Silva, Ana Bettencourt, Sandra Aguiar, Maria Gaspar. Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms. Pharmaceutics. 2021; 13 (3):321.

Chicago/Turabian Style

Magda Ferreira; Sandra Pinto; Frederico Aires-Da-Silva; Ana Bettencourt; Sandra Aguiar; Maria Gaspar. 2021. "Liposomes as a Nanoplatform to Improve the Delivery of Antibiotics into Staphylococcus aureus Biofilms." Pharmaceutics 13, no. 3: 321.

Review article
Published: 22 February 2021 in Drug Delivery and Translational Research
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Worldwide, colon cancer (CC) represents the fourth most common type of cancer and the fifth major cause of cancer-associated deaths. Surgical resection is considered the standard therapeutic choice for CC in early stages. However, in latter stages of the disease, adjuvant chemotherapy is essential for an appropriate management of this pathology. Metal-based complexes displaying cytotoxic properties towards tumor cells emerge as potential chemotherapeutic options. One metallodrug, oxaliplatin, was already approved for clinical use, playing an important role in the treatment of CC patients. Unfortunately, most of the newly designed metal-based complexes exhibit lack of selectivity against cancer cells, low solubility and permeability, high dose-limiting toxicity, and emergence of resistances. Nanodelivery systems enable the incorporation of metallodrugs at adequate payloads, solving the above-referred drawbacks. Moreover, drug delivery systems, depending on their physicochemical properties, are able to release the incorporated material preferentially at affected tissues/organs, enhancing the therapeutic activity in vivo, with concomitant fewer side effects. In this review, the general features and therapeutic management of CC will be addressed, with a special focus on preclinical or clinical studies using metal-based compounds. Furthermore, the use of different nanodelivery systems will also be described as tools to potentiate the therapeutic index of metallodrugs for the management of CC.

ACS Style

Pedro Farinha; Jacinta O. Pinho; Mariana Matias; M. Manuela Gaspar. Nanomedicines in the treatment of colon cancer: a focus on metallodrugs. Drug Delivery and Translational Research 2021, 1 -18.

AMA Style

Pedro Farinha, Jacinta O. Pinho, Mariana Matias, M. Manuela Gaspar. Nanomedicines in the treatment of colon cancer: a focus on metallodrugs. Drug Delivery and Translational Research. 2021; ():1-18.

Chicago/Turabian Style

Pedro Farinha; Jacinta O. Pinho; Mariana Matias; M. Manuela Gaspar. 2021. "Nanomedicines in the treatment of colon cancer: a focus on metallodrugs." Drug Delivery and Translational Research , no. : 1-18.

Journal article
Published: 01 January 2021 in Nanomedicine
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In drug discovery and drug development, it is estimated that around 40% of commercialized and 90% of under-study drugs have inadequate pharmaceutical properties, severely impairing its therapeutic efficacy. Thus, there is a strong demand to find strategies to enhance the delivery of such drugs. Ionic liquids are a novel class of liquids composed of a combination of organic salts that are of particular interest alone or in combination with drug delivery systems. This review is focused on the recent efforts using ionic liquids in drug solubility, formulation and drug delivery with specific emphasis on nanotechnology. The latest developments using hybrid delivery systems obtained upon the combination of drug delivery systems and ionic liquids will also be addressed.

ACS Style

Mariana Amaral; Ana B Pereiro; Maria Manuela Gaspar; Catarina Pinto Reis. Recent advances in ionic liquids and nanotechnology for drug delivery. Nanomedicine 2021, 16, 63 -80.

AMA Style

Mariana Amaral, Ana B Pereiro, Maria Manuela Gaspar, Catarina Pinto Reis. Recent advances in ionic liquids and nanotechnology for drug delivery. Nanomedicine. 2021; 16 (1):63-80.

Chicago/Turabian Style

Mariana Amaral; Ana B Pereiro; Maria Manuela Gaspar; Catarina Pinto Reis. 2021. "Recent advances in ionic liquids and nanotechnology for drug delivery." Nanomedicine 16, no. 1: 63-80.

Journal article
Published: 18 December 2020 in International Journal of Molecular Sciences
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Breast cancer is one of the most frequently diagnosed malignancies and common causes of cancer death in women. Recent studies suggest that environmental exposures to certain chemicals, such as 7,12-Dimethylbenzanthracene (DMBA), a chemical present in tobacco, may increase the risk of developing breast cancer later in life. The first-line treatments for breast cancer (surgery, chemotherapy or a combination of both) are generally invasive and frequently associated with severe side effects and high comorbidity. Consequently, novel approaches are strongly required to find more natural-like experimental models that better reflect the tumors’ etiology, physiopathology and response to treatments, as well as to find more targeted, efficient and minimally invasive treatments. This study proposes the development and an in deep biological characterization of an experimental model using DMBA-tumor-induction in Sprague-Dawley female rats. Moreover, a photothermal therapy approach using a near-infrared laser coupled with gold nanoparticles was preliminarily assessed. The gold nanoparticles were functionalized with Epidermal Growth Factor, and their physicochemical properties and in vitro effects were characterized. DMBA proved to be a very good and selective inductor of breast cancer, with 100% incidence and inducing an average of 4.7 tumors per animal. Epigenetic analysis showed that tumors classified with worst prognosis were hypomethylated. The tumor-induced rats were then subjected to a preliminary treatment using functionalized gold nanoparticles and its activation by laser (650–900 nm). The treatment outcomes presented very promising alterations in terms of tumor histology, confirming the presence of necrosis in most of the cases. Although this study revealed encouraging results as a breast cancer therapy, it is important to define tumor eligibility and specific efficiency criteria to further assess its application in breast cancer treatment on other species.

ACS Style

Eduardo Costa; Tânia Ferreira-Gonçalves; Miguel Cardoso; João M. P. Coelho; Maria Manuela Gaspar; Pedro Faísca; Lia Ascensão; António S. Cabrita; Catarina Pinto Reis; Isabel V. Figueiredo. A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach. International Journal of Molecular Sciences 2020, 21, 9681 .

AMA Style

Eduardo Costa, Tânia Ferreira-Gonçalves, Miguel Cardoso, João M. P. Coelho, Maria Manuela Gaspar, Pedro Faísca, Lia Ascensão, António S. Cabrita, Catarina Pinto Reis, Isabel V. Figueiredo. A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach. International Journal of Molecular Sciences. 2020; 21 (24):9681.

Chicago/Turabian Style

Eduardo Costa; Tânia Ferreira-Gonçalves; Miguel Cardoso; João M. P. Coelho; Maria Manuela Gaspar; Pedro Faísca; Lia Ascensão; António S. Cabrita; Catarina Pinto Reis; Isabel V. Figueiredo. 2020. "A Step Forward in Breast Cancer Research: From a Natural-Like Experimental Model to a Preliminary Photothermal Approach." International Journal of Molecular Sciences 21, no. 24: 9681.

Journal article
Published: 04 December 2020 in Pharmaceutics
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Sambucus nigra L. is widely used in traditional medicine with different applications. However, confirmative studies are strongly required. This study aimed to assess the biological activities of the S. nigra flower’s extract encapsulated into two different types of nanoparticles for optimizing its properties and producing further evidence of its potential therapeutic uses. Different nanoparticles (poly(lactide-co-glycolide, PLGA) and poly-Ɛ-caprolactone (PCL), both with oleic acid, were prepared by emulsification/solvent diffusion and solvent-displacement methods, respectively. Oleic acid was used as a capping agent. After the nanoparticles’ preparation, they were characterized and the biological activities were studied in terms of collagenase, in vitro and in vivo anti-inflammatory, and in vitro cell viability. Rutin and naringenin were found to be the major phenolic compounds in the studied extract. The encapsulation efficiency was higher than 76% and revealed to have an impact on the release of the extract, mainly for the PLGA. Moreover, biochemical and histopathological analyses confirmed that the extract-loaded PLGA-based nanoparticles displayed the highest anti-inflammatory activity. In addition to supporting the previously reported evidence of potential therapeutic uses of S. nigra, these results could draw the pharmaceutical industry’s interest to the novelty of the nanoproducts.

ACS Style

Ana Mota; Noélia Duarte; Ana Serra; António Ferreira; Maria Bronze; Luísa Custódio; Maria Gaspar; Sandra Simões; Patrícia Rijo; Lia Ascensão; Pedro Faísca; Ana Viana; Rui Pinto; Pradeep Kumar; António Almeida; Catarina Reis. Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations. Pharmaceutics 2020, 12, 1181 .

AMA Style

Ana Mota, Noélia Duarte, Ana Serra, António Ferreira, Maria Bronze, Luísa Custódio, Maria Gaspar, Sandra Simões, Patrícia Rijo, Lia Ascensão, Pedro Faísca, Ana Viana, Rui Pinto, Pradeep Kumar, António Almeida, Catarina Reis. Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations. Pharmaceutics. 2020; 12 (12):1181.

Chicago/Turabian Style

Ana Mota; Noélia Duarte; Ana Serra; António Ferreira; Maria Bronze; Luísa Custódio; Maria Gaspar; Sandra Simões; Patrícia Rijo; Lia Ascensão; Pedro Faísca; Ana Viana; Rui Pinto; Pradeep Kumar; António Almeida; Catarina Reis. 2020. "Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations." Pharmaceutics 12, no. 12: 1181.

Journal article
Published: 05 August 2020 in Nanomaterials
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Cancer like melanoma is a complex disease, for which standard therapies have significant adverse side effects that in most cases are ineffective and highly unspecific. Thus, a new paradigm has come with the need of achieving alternative (less invasive) and effective therapies. In this work, biocompatible gold nanoparticles (GNPs) coated with hyaluronic acid and oleic acid were prepared and characterized in terms of size, morphology and cytotoxicity in the presence of Saccharomyces cerevisiae, and two cell lines, the keratinocytes (healthy skin cells, HaCat) and the melanoma cells (B16F10). Results showed that these GNPs absorb within the near-infrared region (750–1400 nm), in the optical therapeutic window (from 650 to 1300 nm), in contrast to other commercial gold nanoparticles, which enables light to penetrate into deep skin layers. A laser emitting in this region was applied and its effect also analyzed. The coated GNPs showed a spherical morphology with a mean size of 297 nm without cytotoxic effects towards yeast and tested cell lines. Nevertheless, after laser irradiation, a reduction of 20% in B16F10 cell line viability was observed. In summary, this work appears to be a promising strategy for the treatment of non-metastatic melanoma or other superficial tumors.

ACS Style

Joana Lopes; João Miguel Pinto Coelho; Pedro Manuel Cardoso Vieira; Ana Silveira Viana; Maria Manuela Gaspar; Catarina Reis. Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials. Nanomaterials 2020, 10, 1536 .

AMA Style

Joana Lopes, João Miguel Pinto Coelho, Pedro Manuel Cardoso Vieira, Ana Silveira Viana, Maria Manuela Gaspar, Catarina Reis. Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials. Nanomaterials. 2020; 10 (8):1536.

Chicago/Turabian Style

Joana Lopes; João Miguel Pinto Coelho; Pedro Manuel Cardoso Vieira; Ana Silveira Viana; Maria Manuela Gaspar; Catarina Reis. 2020. "Preliminary Assays towards Melanoma Cells Using Phototherapy with Gold-Based Nanomaterials." Nanomaterials 10, no. 8: 1536.

Journal article
Published: 27 June 2020 in Industrial Crops and Products
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There is a re-emerging interest in natural products as reputable sources of new active pharmaceutical ingredients. This study synchronously reports in vitro, with more than one cell line, and in vivo biological activities of extracts obtained from Sambucus nigra. Using several solvents and techniques, eighteen extracts were obtained from fresh and dried berries, and fresh flowers. The flavonoid content and identification were determined using HPLC-MS/MS. The extracts were then screened for antioxidant activity, total polyphenol content, collagenase, elastase, tyrosinase and acetylcholinesterase inhibition as well as photoprotection. In vitro and in vivo (murine model) anti-inflammatory activity and cytotoxicity (skin and monocytic cells) were also studied. The most promising extracts were those obtained from fresh flowers using either ultrasounds or methanol. These extracts showed similar results to positive controls, particularly the antioxidant activity (74.5 ± 1.6 %), collagenase inhibition (93.6 ± 0.6 %), photoprotection (Sun Protection Factor >50), in vitro anti-inflammatory activity (96.9 ± 2.9 %), as well as oral/topical anti-inflammatory activity. The ultrasounds/ethanol extract of fresh flowers presented higher collagenase inhibition (88.3 ± 2.8 %) and in vitro anti-inflammatory activity (101.8 ± 1.5 %). Cytotoxicity testing confirmed the safety. Chemical characterization allowed the deduction of a correlation between extract composition and biological activities, suggesting a straightforward application in the development of novel products subject to further investigation.

ACS Style

Ana Henriques Mota; Joana M. Andrade; Maria João Rodrigues; Luísa Custódio; Maria Rosário Bronze; Noélia Duarte; André Baby; João Rocha; Maria Manuela Gaspar; Sandra Simões; Manuela Carvalheiro; Elias Fattal; António José Almeida; Catarina Pinto Reis. Synchronous insight of in vitro and in vivo biological activities of Sambucus nigra L. extracts for industrial uses. Industrial Crops and Products 2020, 154, 112709 .

AMA Style

Ana Henriques Mota, Joana M. Andrade, Maria João Rodrigues, Luísa Custódio, Maria Rosário Bronze, Noélia Duarte, André Baby, João Rocha, Maria Manuela Gaspar, Sandra Simões, Manuela Carvalheiro, Elias Fattal, António José Almeida, Catarina Pinto Reis. Synchronous insight of in vitro and in vivo biological activities of Sambucus nigra L. extracts for industrial uses. Industrial Crops and Products. 2020; 154 ():112709.

Chicago/Turabian Style

Ana Henriques Mota; Joana M. Andrade; Maria João Rodrigues; Luísa Custódio; Maria Rosário Bronze; Noélia Duarte; André Baby; João Rocha; Maria Manuela Gaspar; Sandra Simões; Manuela Carvalheiro; Elias Fattal; António José Almeida; Catarina Pinto Reis. 2020. "Synchronous insight of in vitro and in vivo biological activities of Sambucus nigra L. extracts for industrial uses." Industrial Crops and Products 154, no. : 112709.

Review
Published: 15 June 2020
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Globally, thyroid cancer accounts for 2 % of all cancer diagnoses, and can be classified as well-differentiated or undifferentiated. Currently, differentiated thyroid carcinomas have good prognoses, and can be treated with a combination of therapies, including surgical thyroidectomy, radioactive iodine therapy and hormone-based therapy. On the other hand, anaplastic thyroid carcinoma, a subtype of undifferentiated thyroid carcinoma characterized by the loss of thyroid-like phenotype and function, does not respond to either radioactive iodine or hormone therapies. In most cases, anaplastic thyroid carcinomas are diagnosed in later stages of the disease, deeming them inoperable, and showing poor response rates to systemic chemotherapy. Recently, treatment courses using multiple-target agents are being explored and clinical trials have shown very promising results, such as overall survival rates, progression-free survival and tumor shrinkage. This review is focused on thyroid carcinomas, with particular focus on anaplastic thyroid carcinoma, exploring its undifferentiated nature. Special interest will be given to the treatment approaches currently available and respective obstacles or drawbacks. Our purpose is to contribute to understand why this malignancy presents low responsiveness to current treatments, while overviewing novel therapies and clinical trials.

ACS Style

Mariana N. Amaral; Ricardo A. Afonso; Maria Manuela Gaspar; Catarina Pinto Reis. Anaplastic thyroid cancer: How far can we go? 2020, 19, 800 -812.

AMA Style

Mariana N. Amaral, Ricardo A. Afonso, Maria Manuela Gaspar, Catarina Pinto Reis. Anaplastic thyroid cancer: How far can we go? . 2020; 19 ():800-812.

Chicago/Turabian Style

Mariana N. Amaral; Ricardo A. Afonso; Maria Manuela Gaspar; Catarina Pinto Reis. 2020. "Anaplastic thyroid cancer: How far can we go?" 19, no. : 800-812.

Review article
Published: 08 June 2020 in Drug Delivery and Translational Research
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Bone infections caused by Staphylococcus aureus are a major concern in medical care, particularly when associated with orthopedic-implant devices. The ability of the bacteria to form biofilms and their capacity to invade and persist within osteoblasts turn the infection eradication into a huge challenge. The reduction of antibiotic penetration through bacterial biofilms associated with the presence of persistent cells, ability to survive in the host, and high tolerance to antibiotics are some of the reasons for the difficult treatment of these infections. Effective therapeutic approaches are urgently needed. In this sense, lipid-based nanosystems, such as liposomes, have been investigated as an innovative and alternative strategy for the treatment of implant-associated S. aureus infections, due to their preferential accumulation at infected sites and interaction with S. aureus. This review highlights the recent advances on antibiotic-loaded liposome formulations both in vitro and in vivo and how the interaction with S. aureus biofilms may be improved by modulating the liposomal external surface. Graphical

ACS Style

Magda Ferreira; Sandra Aguiar; Ana Bettencourt; Maria Manuela Gaspar. Lipid-based nanosystems for targeting bone implant-associated infections: current approaches and future endeavors. Drug Delivery and Translational Research 2020, 11, 72 -85.

AMA Style

Magda Ferreira, Sandra Aguiar, Ana Bettencourt, Maria Manuela Gaspar. Lipid-based nanosystems for targeting bone implant-associated infections: current approaches and future endeavors. Drug Delivery and Translational Research. 2020; 11 (1):72-85.

Chicago/Turabian Style

Magda Ferreira; Sandra Aguiar; Ana Bettencourt; Maria Manuela Gaspar. 2020. "Lipid-based nanosystems for targeting bone implant-associated infections: current approaches and future endeavors." Drug Delivery and Translational Research 11, no. 1: 72-85.

Journal article
Published: 27 April 2020 in Biomolecules
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Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (

ACS Style

Mariana Amaral; Ana Sofia Martins; José Catarino; Pedro Faísca; Pradeep Kumar; João F. Pinto; Rui Pinto; Isabel Correia; Lia Ascensão; Ricardo A. Afonso; M. Manuela Gaspar; Adília J. Charmier; Isabel Vitória Figueiredo; Catarina Pinto Reis. How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models. Biomolecules 2020, 10, 675 .

AMA Style

Mariana Amaral, Ana Sofia Martins, José Catarino, Pedro Faísca, Pradeep Kumar, João F. Pinto, Rui Pinto, Isabel Correia, Lia Ascensão, Ricardo A. Afonso, M. Manuela Gaspar, Adília J. Charmier, Isabel Vitória Figueiredo, Catarina Pinto Reis. How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models. Biomolecules. 2020; 10 (5):675.

Chicago/Turabian Style

Mariana Amaral; Ana Sofia Martins; José Catarino; Pedro Faísca; Pradeep Kumar; João F. Pinto; Rui Pinto; Isabel Correia; Lia Ascensão; Ricardo A. Afonso; M. Manuela Gaspar; Adília J. Charmier; Isabel Vitória Figueiredo; Catarina Pinto Reis. 2020. "How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models." Biomolecules 10, no. 5: 675.

Journal article
Published: 06 April 2020 in Nanomaterials
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Cancer is a major health concern and the prognosis is often poor. Significant advances in nanotechnology are now driving a revolution in cancer detection and treatment. The goal of this study was to develop a novel hybrid nanosystem for melanoma treatment, integrating therapeutic and magnetic targeting modalities. Hence, we designed long circulating and pH-sensitive liposomes loading both dichloro(1,10-phenanthroline) copper (II) (Cuphen), a cytotoxic metallodrug, and iron oxide nanoparticles (IONPs). The synthetized IONPs were characterized by transmission electron microscopy and dynamic light scattering. Lipid-based nanoformulations were prepared by the dehydration rehydration method, followed by an extrusion step for reducing and homogenizing the mean size. Liposomes were characterized in terms of incorporation parameters and mean size. High Cuphen loadings were obtained and the presence of IONPs slightly reduced Cuphen incorporation parameters. Cuphen antiproliferative properties were preserved after association to liposomes and IONPs (at 2 mg/mL) did not interfere on cellular proliferation of murine and human melanoma cell lines. Moreover, the developed nanoformulations displayed magnetic properties. The absence of hemolytic activity for formulations under study demonstrated their safety for parenteral administration. In conclusion, a lipid-based nanosystem loading the cytotoxic metallodrug, Cuphen, and displaying magnetic properties was successfully designed.

ACS Style

Nuno Cruz; Jacinta Oliveira Pinho; Graça Soveral; Lia Ascensão; Nuno Matela; Catarina Reis; Maria Manuela Gaspar. A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy. Nanomaterials 2020, 10, 693 .

AMA Style

Nuno Cruz, Jacinta Oliveira Pinho, Graça Soveral, Lia Ascensão, Nuno Matela, Catarina Reis, Maria Manuela Gaspar. A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy. Nanomaterials. 2020; 10 (4):693.

Chicago/Turabian Style

Nuno Cruz; Jacinta Oliveira Pinho; Graça Soveral; Lia Ascensão; Nuno Matela; Catarina Reis; Maria Manuela Gaspar. 2020. "A Novel Hybrid Nanosystem Integrating Cytotoxic and Magnetic Properties as a Tool to Potentiate Melanoma Therapy." Nanomaterials 10, no. 4: 693.

Journal article
Published: 02 April 2020 in International Journal of Molecular Sciences
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Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.

ACS Style

Catarina Pimpão; Inês V. Da Silva; Andreia F. Mósca; Jacinta O. Pinho; Maria Manuela Gaspar; Nadiia I. Gumerova; Annette Rompel; Manuel Aureliano; Graça Soveral. The Aquaporin-3-Inhibiting Potential of Polyoxotungstates. International Journal of Molecular Sciences 2020, 21, 2467 .

AMA Style

Catarina Pimpão, Inês V. Da Silva, Andreia F. Mósca, Jacinta O. Pinho, Maria Manuela Gaspar, Nadiia I. Gumerova, Annette Rompel, Manuel Aureliano, Graça Soveral. The Aquaporin-3-Inhibiting Potential of Polyoxotungstates. International Journal of Molecular Sciences. 2020; 21 (7):2467.

Chicago/Turabian Style

Catarina Pimpão; Inês V. Da Silva; Andreia F. Mósca; Jacinta O. Pinho; Maria Manuela Gaspar; Nadiia I. Gumerova; Annette Rompel; Manuel Aureliano; Graça Soveral. 2020. "The Aquaporin-3-Inhibiting Potential of Polyoxotungstates." International Journal of Molecular Sciences 21, no. 7: 2467.