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2016
Roma-Rodrigues, C, Heuer-Jungemann A, Fernandes AR, Kanaras AG, Baptista PV.  2016.  Peptide-coated gold nanoparticles for modulation of angiogenesis in vivo, 2016. 11 Abstract
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Raposo, LR, Roma-Rodrigues C, Faísca P, Alves M, Henriques J, Carvalheiro MC, Corvo LM, Baptista PV, Pombeiro AJL, Fernandes AR.  2016.   Immortalization and characterization of a new canine mammary tumor cell line FR37-CMT. J. Veterinary and Comparative Oncology. AbstractWebsite

Here we describe the establishment of a new canine mammary tumour (CMT) cell line, FR37-CMT that does not show dependence on female hormonal signaling to induce tumour xenografts in NOD-SCID mice. FR37-CMT cell line has a stellate or fusiform shape, displays the ability to reorganize the collagen matrix, expresses vimentin, CD44 and shows the loss of E-cadherin which is considered a fundamental event in epithelial to mesenchymal transition (EMT). The up-regulation of ZEB1, the detection of phosphorylated ERK1/2 and the downregulation of DICER1 and miR-200c are also in accordance with the mesenchymal characteristics of FR37-CMT cell line. FR37-CMT shows a higher resistance to cisplatin (IC50>50 µM) and to doxorubicin (IC50>5.3 µM) compared with other CMT cell lines. These results support the use of FR37-CMT as a new CMT model that may assist the understanding of the molecular mechanisms underlying EMT, CMT drug resistance, fostering the development of novel therapies targeting CMT.

Martins, M, Baptista PV, Mendo AS, Correia C, Videira P, Rodrigues AS, Muthukumaran J, Santos-Silva T, Silva A, da Silva FGMC, Gigante J, Duarte A, Pombeiro AJL, Fernandes AR.  2016.   In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(IV) complex. Molecular BioSystems. (12) AbstractWebsite

Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(IV) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(IV) complex with an aromatic oximehydroxamic acid group [nBu2Sn(L)]3(H2L = N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) – MG85 – and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts.

Vinhas, R, Correia C, Ribeiro P, Lourenço A, de Sousa AB, Fernandes AR, Baptista PV.  2016.  Colorimetric assessment of BCR-ABL1 transcripts in clinical samples via gold nanoprobes. Analytical and Bioanalytical Chemistry. 408(19):5277–5284. AbstractWebsite

Gold nanoparticles functionalized with thiolated oligonucleotides (Au-nanoprobes) have been used in a range of applications for the detection of bioanalytes of interest, from ions to proteins and DNA targets. These detection strategies are based on the unique optical properties of gold nanoparticles, in particular, the intense color that is subject to modulation by modification of the medium dieletric. Au-nanoprobes have been applied for the detection and characterization of specific DNA sequences of interest, namely pathogens and disease biomarkers. Nevertheless, despite its relevance, only a few reports exist on the detection of RNA targets. Among these strategies, the colorimetric detection of DNA has been proven to work for several different targets in controlled samples but demonstration in real clinical bioanalysis has been elusive. Here, we used a colorimetric method based on Au-nanoprobes for the direct detection of the e14a2 BCR-ABL fusion transcript in myeloid leukemia patient samples without the need for retro-transcription. Au-nanoprobes directly assessed total RNA from 38 clinical samples, and results were validated against reverse transcription-nested polymerase chain reaction (RT-nested PCR) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The colorimetric Au-nanoprobe assay is a simple yet reliable strategy to scrutinize myeloid leukemia patients at diagnosis and evaluate progression, with obvious advantages in terms of time and cost, particularly in low- to medium-income countries where molecular screening is not routinely feasible.

Vinhas, R, Cordeiro M, Pedrosa P, Fernandes AR, Baptista PV.  2016.  Current trends in molecular diagnostics of chronic myeloid leukemia. Leukemia & Lymphoma. :1-14. AbstractWebsite

Nearly 1.5 million people worldwide suffer from chronic myeloid leukemia (CML), characterized by the genetic translocation t(9;22)(q34;q11.2), involving the fusion of the Abelson oncogene (ABL1) with the breakpoint cluster region (BCR) gene. Early onset diagnosis coupled to current therapeutics allow for a treatment success rate of 90, which has focused research on the development of novel diagnostics approaches. In this review, we present a critical perspective on current strategies for CML diagnostics, comparing to gold standard methodologies and with an eye on the future trends on nanotheranostics.

Cordeiro, M, Carlos FF, Pedrosa P, Lopez A, Baptista PV.  2016.  Gold Nanoparticles for Diagnostics: Advances towards Points of Care. Diagnostics. 6(4):43. AbstractWebsite

The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor, most platforms have yet to reach maturity and make their way into clinics or points of care (POC). Here, we present an overview of emerging and available molecular diagnostics using AuNPs for biomedical sensing that are currently being translated to the clinical setting.

Corvo, L, Mendo AS, Figueiredo S, Larguinho M, Gaspar R, Baptista PV, Fernandes AR.  2016.  Liposomes as delivery system of a Sn(IV) compound for cancer therapy. Pharmaceutical Research. 6(33):1351-8. AbstractWebsite

PROPOSE:
Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu2Sn(L)]3 (L=N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity, induces apoptosis and oxidative stress, and causes destabilization of tubulin microtubules, particularly in colorectal carcinoma cells. Despite the great efficacy towards cancer cells, this complex still shows some cytotoxicity to healthy cells. Targeted delivery of this complex specifically towards cancer cells might foster cancer treatment.
METHODS:
MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated.
RESULTS:
Encapsulation of MG85 complex in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer cell death when compared to free complex, whilst decreasing cytotoxicity in non-tumor cells. Labeling of liposomes with Rhodamine allowed assessing internalization in cells, which showed significant cell uptake after 6 h of incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes that displayed higher internalization rate in HCT116 cells when compared with non-targeted liposomes, which seems to internalize via active binding of Cetuximab to cells.
CONCLUSIONS:
The proposed formulation open new avenues in the design of innovative transition metal-based vectorization systems that may be further extended to other novel metal complexes towards the improvement of their anti-cancer efficacy, which is usually hampered by solubility issues and/or toxicity to healthy tissues.

Mendes, R, Carreira B, Baptista PV, Fernandes AR.  2016.  Non-small lung cancer biomarkers and targeted therapy - two faces of the same coin fostered by Nanotechnology. Expert Review of Precision Medicine and Drug Development. 1(2):155-168. AbstractWebsite

Lung cancer is the leading cause of cancer-related mortality in the world, non-small lung cancer (NSCLC) is the most frequent subtype (85% of the cases). Within this subtype, adenocarcinoma and squamous cell carcinoma are the most frequent. New therapeutic strategies based on targeted delivery of drugs have relied on the use of biomarkers derived from the patients’ molecular profiling. Several biomarkers have been found to be useful for use as targets for precision therapy in NSCLC, such as mutations in the epidermal growth factor receptor, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, anaplastic lymphoma kinase, mesenchymal-epithelial transition factor receptor tyrosine kinase, BRAF, c-ros oncogene 1, P53 and phosphatase with tensin homology. Current developments in Nanomedicine have allowed for multifunctional systems capable of delivering therapeutics with increased precision to the target site/tissue, while simultaneously assisting in diagnosis. Here, we review the use of biomarkers in nanotechnology translation in NSCLC management.

Roma-Rodrigues, C, Heuer-Jungemann A, Fernandes AR, Kanaras AG, Baptista PV.  2016.  Peptide coated gold nanoparticles for in vivo targeting of angiogenesis. International J. Nanomedicine. (11):2633–2639. AbstractWebsite

In this work, peptides designed to selectively interact with cellular receptors involved in the regulation of angiogenesis were anchored to oligo-ethylene glycol-capped gold nanoparticles (AuNPs) and used to evaluate the modulation of vascular development using an ex ovo chick chorioallantoic membrane assay. These nanoparticles alter the balance between naturally secreted pro- and antiangiogenic factors, under various biological conditions, without causing toxicity. Exposure of chorioallantoic membranes to AuNP–peptide activators of angiogenesis accelerated the formation of new arterioles when compared to scrambled peptide-coated nanoparticles. On the other hand, antiangiogenic AuNP–peptide conjugates were able to selectively inhibit angiogenesis in vivo. We demonstrated that AuNP vectorization is crucial for enhancing the effect of active peptides. Our data showed for the first time the effective control of activation or inhibition of blood vessel formation in chick embryo via AuNP-based formulations suitable for the selective modulation of angiogenesis, which is of paramount importance in applications where promotion of vascular growth is desirable (eg, wound healing) or ought to be contravened, as in cancer development.

Silva, M, Silva Z, Marques G, Ferro T, Gonçalves M, Monteiro M, van Vliet SJ, Mohr E, Lino AC, Fernandes AR, Lima FA, van Kooyk Y, Matos T, Tadokoro CE, Videira PA.  2016.  Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses. Oncotarget . AbstractWebsite

Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs’ ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

Ma, Z, Zhang B, da Silva FGMC, Mendo AS, Silva J, Baptista PV, Fernandes AR, Pombeiro AJL.  2016.  Synthesis, Characterization, Thermal Properties and Antiproliferative Potential of Copper(II) 4′-phenyl-terpyridine Compounds. Dalton Transations. (12) AbstractWebsite

Reactions between 4′-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]·MeOH (4·MeOH) and [Cu(p-OCOC6H4OH)2L]·2H2O (5·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2–5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π⋯π stacking interactions could also be found in 2–5 (in the 3.569–3.651 Å range and involving solely the pyridyl rings). Medium–strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

Sutradhar, M, Fernandes AR, Silva J, Mahmudov KT, da Silva FGMC, Pombeiro AJL.  2016.  Water soluble heterometallic potassium-dioxidovanadium(V) (K+/VO3+) complexes as potential antiproliferative agents. J Inorg Biochem. (155):17-25. AbstractWebsite

Two water soluble heterometallic potassium–dioxidovanadium polymers, [KVO2(L1)]n (1) and [KVO2(L2)(H2O)]n (2) [H2L1= (2,3-dihydroxybenzylidene)-2-hydroxybenzohydrazide and H2L2=(2,3-dihydroxybenzylidene)benzohydrazide], have been synthesized and characterized by IR, NMR, elemental analysis and single crystal X-ray diffraction. The antiproliferative potentials of 1 and 2 were examined towards human colorectal carcinoma (HCT116), and lung (A549) and breast (MCF7) adenocarcinoma cell lines. 1 exhibits a high cytotoxic activity against colorectal carcinoma cells (HCT116), with IC50 lower than those for cisplatin.

2015
Pedrosa, P, Vinhas R, Fernandes A, Baptista PV.  2015.  Gold Nanotheranostics: Proof-of-Concept or Clinical Tool?, 2015/10/27/accep Nanomaterials. 5(4)(Selvan, Subramanian Tamil, Ed.).:1853-1879.: MDPI AbstractWebsite

Nanoparticles have been making their way in biomedical applications and personalized medicine, allowing for the coupling of diagnostics and therapeutics into a single nanomaterial—nanotheranostics. Gold nanoparticles, in particular, have unique features that make them excellent nanomaterials for theranostics, enabling the integration of targeting, imaging and therapeutics in a single platform, with proven applicability in the management of heterogeneous diseases, such as cancer. In this review, we focus on gold nanoparticle-based theranostics at the lab bench, through pre-clinical and clinical stages. With few products facing clinical trials, much remains to be done to effectively assess the real benefits of nanotheranostics at the clinical level. Hence, we also discuss the efforts currently being made to translate nanotheranostics into the market, as well as their commercial impact.

Vinhas, R, Tolmatcheva A, Canto R, Ribeiro P, Lourenço A, de Sousa AB, Baptista PV, Fernandes AR.  2015.   A novel mutation in the CEBPA gene in a patient with acute myeloid leukemia. Leukimia Lymphoma. :711-713.Website
Mendo, AS, Figueiredo S, Roma-Rodrigues C, Videira PA, Ma Z, Diniz M, Larguinho M, Costa PM, Pombeiro AJL, Baptista PV, Fernandes AR.  2015.   Characterization of antiproliferative potential and biological targets of a copper complex containing 4’-phenyl terpyridine. JBIC . (20):935. AbstractWebsite

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

I.C.J.Palma, S, Carvalho A, Silva J, Fernandes AR, del Puerto-Morales M, Roque ACA.  2015.  Covalent coupling of gum arabic onto superparamagnetic iron oxide nanoparticles for MRI cell labeling: physiochemical and in vitro characterization. Contrast Media and Molecular Imaging. AbstractWebsite

Gum arabic (GA) is a hydrophilic composite polysaccharide derived from exudates of Acacia senegal and Acacia seyal trees. It is biocompatible, possesses emulsifying and stabilizing properties and has been explored as coating agent of nanomaterials for biomedical applications, namely magnetic nanoparticles (MNPs). Previous studies focused on the adsorption of GA onto MNPs produced by co-precipitation methods. In this work, MNPs produced by a thermal decomposition method, known to produce uniform particles with better crystalline properties, were used for the covalent coupling of GA through its free amine groups, which increases the stability of the coating layer. The MNPs were produced by thermal decomposition of Fe(acac)3 in organic solvent and, after ligand-exchange with meso-2,3-dimercaptosuccinic acid (DMSA), GA coating was achieved by the establishment of a covalent bond between DMSA and GA moieties. Clusters of several magnetic cores entrapped in a shell of GA were obtained, with good colloidal stability and promising magnetic relaxation properties (r2 /r1 ratio of 350). HCT116 colorectal carcinoma cell line was used for in vitro cytotoxicity evaluation and cell-labeling efficiency studies. We show that, upon administration at the respective IC50 , GA coating enhances MNP cellular uptake by 19 times compared to particles bearing only DMSA moieties. Accordingly, in vitro MR images of cells incubated with increasing concentrations of GA-coated MNP present dose-dependent contrast enhancement. The obtained results suggest that the GA magnetic nanosystem could be used as a MRI contrast agent for cell-labeling applications.

Vinhas, R, Cordeiro M, Carlos FF, Mendo S, Fernandes AR, Figueiredo S, Baptista PV.  2015.  Gold nanoparticle-based theranostics: disease diagnostic and treatment using a single nanomaterial. J. Nanobiosensors in Disease Diagnosis. 11-23(4) AbstractWebsite

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

Martins, P, Jesus J, Santos S, Raposo LR, Roma-Rodrigues C, Baptista PV, Fernandes AR.  2015.  Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine’s Tool Box. Molecules. 9(20):16852-16891. AbstractWebsite

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

Roma-Rodrigues, C, Barroco C, Raposo LR, Costa MN, Fortunato E, Baptista PV, Fernandes AR, Santos-Sanches I.  2015.  Infection of human keratinocytes by Streptococcus dysgalactiae subspecies dysgalactiae isolated from milk of the bovine udder.. Microbes and Infection. 4(18):290-3. AbstractWebsite

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) are considered exclusive animal pathogens; however, a putative zoonotic upper limb cellulitis, a prosthetic joint infection and an infective endocarditis were described in humans. To unravel if bovine SDSD isolates are able to infect human cells, the adherence and internalization to human primary keratinocytes of two bovine SDSD strains isolated from milk collected from udder were analyzed. Bacterial adhesion assays and confocal microscopy indicate a high adherence and internalization of SDSD isolates to human cells, suggesting for the first time the ability of bovine isolates to infect human cells.

Coimbra, J, Mota C, Santos S, Baptista PV, Fernandes AR.  2015.  Inorganic Compounds Going NANO. Annals of Medicinal Chemistry and Research. 2(1)medicinalchemistry-1-1010.pdf
Roma-Rodrigues, C, Raposo LR, Fernandes AR.  2015.  microRNAs based therapy of Hypertrophic cardiomyopathy: the road traveled so far. BioMed Research International. :983290. AbstractWebsite

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by variable expressivity, age penetrance, and a high heterogeneity. The transcriptional profile (miRNAs, mRNAs), epigenetic modifications, and posttranslational modifications seem to be highly relevant for the onset of the disease. miRNAs, small noncoding RNAs with 22 nucleotides, have been implicated in the regulation of cardiomyocyte function, being differentially expressed in several heart diseases, including HCM. Moreover, a different miRNA expression profile in the various stages of HCM development is also observed. This review summarizes the current knowledge of the profile of miRNAs characteristic of asymptomatic to overt HCM patients, discussing alongside their potential use for diagnosis and therapy. Indeed, the stability and specificity of miRNAs make them suitable targets for use as biomarkers for diagnosis and prognosis and as therapeutical targets.

Restani, RB, Conde J, Pires RF, Martins P, Fernandes AR, Baptista PV, Bonifácio VDB, Aguiar-Ricardo A.  2015.  POxylated polyurea dendrimers: Smart core-shell vectors with IC50 lowering capacity. Macromol. Biosci.. AbstractWebsite

The design and preparation of highly efficient drug delivery platforms using green methodologies is at the forefront of nanotherapeutics research. POxylated polyurea dendrimers are efficiently synthesized using a supercritical-assisted polymerization in carbon dioxide. These fluorescent, pH-responsive and water-soluble core-shell smart nanocarriers show low toxicity in terms of cell viability and absence of glutathione depletion, two of the major side effect limitations of current vectors. The materials are also found to act as good transfection agents, through a mechanism involving an endosomal pathway, being able to reduce 100-fold the IC50 of paclitaxel.

Palma, SICJ, Rodrigues CAV, Freitas F, Carvalho A, Fernandes AR, del Morales MP, Cabral JMS, Roque ACA.  2015.  A value-added exopolysaccharide as a coating agent for MRI nanoprobes. Nanoscale. (7):14272-83. AbstractWebsite

Fucopol, a fucose-containing exopolysaccharide (EPS) produced by the bacterium Enterobacter A47 DSM 23139 using glycerol as a carbon source, was employed as a new coating material for iron oxide magnetic nanoparticles (MNPs). The coated particles were assessed as nanoprobes for cell labeling by Magnetic Resonance Imaging (MRI). The MNPs were synthesized by a thermal decomposition method and transferred to an aqueous medium by a ligand-exchange reaction with meso-2,3-dimercaptosuccinic acid (DMSA). Covalent binding of EPS to DMSA-stabilized nanoparticles (MNP–DMSA) resulted in a hybrid magnetic–biopolymeric nanosystem (MNP–DMSA–EPS) with a hydrodynamic size of 170 nm, a negative surface charge under physiological conditions and transverse to longitudinal relaxivity ratio, r2/r1, of 148. In vitro studies with two human cell lines (colorectal carcinoma – HCT116 – and neural stem/progenitor cells – ReNcell VM) showed that EPS promotes internalization of nanoparticles in both cell lines. In vitro MRI cell phantoms showed a superior performance of MNP–DMSA–EPS in ReNcell VM, for which the iron dose-dependent MRI signal drop was obtained at relatively low iron concentrations (12–20 μg Fe per ml) and short incubation times. Furthermore, ReNcell VM multipotency was not affected by culture in the presence of MNP–DMSA or MNP–DMSA–EPS for 14 days. Our study suggests that Fucopol-coated MNPs represent useful cell labeling nanoprobes for MRI.

2014
Roma-Rodrigues, C, Fernandes AR.  2014.  Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy, 2014/10/03. The Application of Clinical Genetics. 7:195-208.: Dove Medical Press AbstractWebsite

Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is mainly due to insufficient knowledge on the mechanisms involved in the onset of HCM. Tissue engineering alongside regenerative medicine coupled with nanotherapeutics may allow fulfillment of those gaps, together with screening of novel therapeutic drugs and target delivery systems.

F. S. Silva, T, M. D. R. S. Martins L, Guedes da Silva FMC, Kuznetsov ML, Fernandes AR, Silva A, Pan C-J, Lee J-F, Hwang B-J, J. L. Pombeiro A.  2014.  Cobalt Complexes with Pyrazole Ligands as Catalyst Precursors for the Peroxidative Oxidation of Cyclohexane: X-ray Absorption Spectroscopy Studies and Biological Applications, 2014/04/01. Chemistry – An Asian Journal. 9(4):1132-1143.: WILEY-VCH Verlag AbstractWebsite
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