Publications by authors named "Clara Marquina"

20 Publications

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Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029.

Eur J Prev Cardiol 2021 Mar 4. Epub 2021 Mar 4.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne 3004, Australia.

Aims: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia.

Methods And Results: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion.

Conclusion: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease.
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http://dx.doi.org/10.1093/eurjpc/zwab001DOI Listing
March 2021

The economic impact of familial hypercholesterolemia on productivity.

J Clin Lipidol 2020 Nov - Dec;14(6):799-806.e3. Epub 2020 Aug 17.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Background: Familial hypercholesterolemia (FH) is a common inherited cause for premature coronary artery disease that increases suffering and disability in affected people. However, the extent to which FH impacts work productivity at a population level is unclear.

Objective: We aimed to quantify the burden of heterozygous FH (HeFH) in terms of productivity-adjusted life years (PALYs) lost to HeFH in Australia.

Methods: A life-table model was constructed to quantify years of life and PALYs lived by Australians with HeFH (prevalence 1 in 300) and of working age (aged 20-69 years). Follow-up was simulated until age 70 years. The model was then resimulated, but assuming the cohort did not have HeFH. Increased cardiovascular mortality and reduction in productivity attributable to HeFH were sourced from published data. Differences in total years of life, quality-adjusted life years, and PALYs lived by the "HeFH cohort" and the same cohort without HeFH ("non-HeFH cohort") reflected the quality-adjusted life years and PALYs lost due to HeFH. All future costs and outcomes were discounted by 5% annually.

Results: In 2017, an estimated 51,587 people of working age in Australia (0.33%) had HeFH. Over their working lifetime, we predicted that 2950 excess cardiovascular deaths occurred in the current Australian population of working age individuals with HeFH, resulting in a loss of 24,727 years of life. In terms of productivity, HeFH led to the loss of 24,954 PALYs over the working lifetime. Based on gross domestic product (GDP) per full-time equivalent worker, this equated to a total of AUD 5.23 billion in lost GDP over the working lifetime, with an average of AUD 101,366 lost per person. A relative reduction of 20% in cardiovascular deaths (as can be achieved with adequate cholesterol control) would lead to 1113 PALYs and AUD 233 million in GDP saved in the HeFH cohort.

Conclusion: The impact of HeFH on work productivity is significant. Screening and prevention strategies tailored early in life are likely to exert not only a positive impact on health but also the economy.
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http://dx.doi.org/10.1016/j.jacl.2020.08.004DOI Listing
August 2020

Early Pregnancy Vitamin D Binding Protein Is Independently Associated with the Development of Gestational Diabetes: A Retrospective Cohort Study.

J Clin Med 2020 Jul 10;9(7). Epub 2020 Jul 10.

Monash Centre for Health Research and Implementation (MCHRI) and Centre of Cardiovascular Research and Education in Therapeutics (CCRET), School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka, Grove, VIC 3168, Australia.

Background: Vitamin D-binding protein (VDBP) has been implicated in several adverse pregnancy outcomes either directly or indirectly via influencing the concentrations of biologically active vitamin D metabolites. However, human studies exploring these metabolites in pregnancy remain sparse. Here, we examine whether VDBP and total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D) metabolites in early pregnancy are associated with subsequent adverse pregnancy outcomes.

Methods: We conducted a retrospective analysis of 304 pregnant women in early pregnancy (<20 weeks gestation). The demographic characteristics, anthropometric data, and total 25(OH)D were measured and plasma or serum samples were collected and bio-banked. Using these samples, we measured VDBP (polyclonal ELISA) and albumin (automated colorimetry), and calculated free and bioavailable 25(OH)D using validated formulae. Pregnancy outcomes were derived from scanned medical records. Regression models were used to analyse the relationships between vitamin D metabolites in early pregnancy and subsequent pregnancy outcomes (gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth), with adjustment for predetermined clinically relevant maternal factors including age, body mass index (BMI), and ethnicity.

Results: Lower VDBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26-28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), = 0.015). This finding remained significant after adjustment for maternal covariates including age, BMI, and ethnicity ( = -0.003, = 0.03). Lower total, free and bioavailable 25(OH)D, but not VDBP, were associated with a shorter length of gestation, but only the relationship with total 25(OH)D remained significant after adjustment for the above maternal covariates ( = 0.02, = 0.006).

Conclusions: This is the first study to examine VDBP, and total, free and bioavailable 25(OH)D in relation to pregnancy outcomes in a well characterised multi-ethnic cohort of pregnant women. Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively; however, further investigations using large-scale prospective studies are needed to confirm our findings.
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http://dx.doi.org/10.3390/jcm9072186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408791PMC
July 2020

Carnosine and histidine-containing dipeptides improve dyslipidemia: a systematic review and meta-analysis of randomized controlled trials.

Nutr Rev 2020 11;78(11):939-951

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Context: Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required.

Objective: Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines.

Data Sources: The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls.

Data Extraction: Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome.

Data Analysis: A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], -0.32 mmol/L [95%CI, -0.57 to -0.07], P = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, -0.14 mmol/L [95%CI, -0.20 to -0.08], P < 0.001) compared with controls. In studies using carnosine, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups.

Conclusions: Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases.

Systemic Review Registration: PROSPERO registration no.: CRD42017075354.
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http://dx.doi.org/10.1093/nutrit/nuaa022DOI Listing
November 2020

Unraveling the mechanism of the one-pot synthesis of exchange coupled Co-based nano-heterostructures with a high energy product.

Nanoscale 2020 Jul 25;12(26):14076-14086. Epub 2020 Jun 25.

ICCOM - CNR, I-50019 Sesto Fiorentino (FI), Italy. and Dept. of Chemistry "U. Schiff", University of Florence and INSTM, I-50019 Sesto Fiorentino (FI), Italy.

The development of reproducible protocols to synthesize hard/soft nano-heterostructures (NHSs) with tailored magnetic properties is a crucial step to define their potential application in a variety of technological areas. Thermal decomposition has proved to be an effective tool to prepare such systems, but it has been scarcely used so far for the synthesis of Co-based metal/ferrite NHSs, despite their intriguing physical properties. We found a new approach to prepare this kind of nanomaterial based on a simple one-pot thermal decomposition reaction of metal-oleate precursors in the high boiling solvent docosane. The obtained NHSs are characterized by the coexistence of Co metal and Co doped magnetite and are highly stable in an air atmosphere, thanks to the passivation of the metal with a very thin oxide layer. The investigation of the influence of the metal precursor composition (a mixed iron-cobalt oleate), of the ligands (oleic acid and sodium oleate) and of the reaction time on the chemical and structural characteristics of the final product, allowed us to rationalize the reaction pathway and to determine the role of each parameter. In particular, the use of sodium oleate is crucial to obtain a metal phase in the NHSs. In such a way, the one-pot approach proposed here allows the fine control of the synthesis, leading to the formation of stable, high performant, metal/ferrite NHSs with tailored magnetic properties. For instance, the room temperature maximum energy product was increased up to 19 kJ m by tuning the Co content in the metal precursor.
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http://dx.doi.org/10.1039/d0nr01361gDOI Listing
July 2020

Novel Treatment Strategies for Secondary Prevention of Cardiovascular Disease: A Systematic Review of Cost-Effectiveness.

Pharmacoeconomics 2020 10;38(10):1095-1113

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, VIC, 3004, Australia.

Background: New pharmacological therapies for the treatment of cardiovascular disease (CVD) have emerged in recent years. The high rates of CVD and the need for long-term treatment to decrease risk factors makes cost-effectiveness crucial for their successful long-term implementation.

Objective: This study assessed cost-effectiveness studies of novel pharmacological treatments (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, omega-3 polyunsaturated fatty acids [n-3 PUFAs], and the cardiovascular polypill) compared with standard care for the secondary prevention of CVD.

Methods: We searched seven databases and the reference list of selected literature reviews for eligible cost-effective analyses (CEA) published between January 2009 and January 2020 that evaluated the above novel treatments versus standard care. Two independent reviewers performed the screening and evaluation in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement. Cost results were adapted to 2018 US dollars (US$) to facilitate comparisons between studies. Consideration of cost-effectiveness was based on the original study criteria.

Results: Thirty-two studies were included in this review, most of them adopting a healthcare perspective. Studies evaluating ezetimibe, PCSK9 inhibitors and n-3 PUFAs assessed their addition to standard care compared with standard care alone, while studies analysing the polypill evaluated the replacement of multiple monotherapies for a fixed-dose combination. Ten studies reported on ezetimibe, fifteen evaluated PCSK9 inhibitors, five focused on n-3 PUFAs and seven on the polypill. From a healthcare perspective, ezetimibe was cost effective in 62.5% of the studies (incremental cost-effectiveness ratios [ICERs] ranged from US$27,195 to US$204,140), n-3 PUFAs in 60% (ICERs from US$57,128 to US$139,082) and the cardiovascular polypill in 100% (ICERs from dominant to US$30,731) compared with standard care. Conversely, only 10% of the studies considered PCSK9 inhibitors cost effective compared with standard care from a healthcare perspective (ICERs ranged from US$231,119 to US$1,223,831). Additionally, ezetimibe was cost effective in 50% of the studies, PCSK9 inhibitors in 33% and the polypill in 50% of the studies adopting a societal perspective. The key model-related parameters predicting cost-effectiveness included drug cost, time horizon, and the baseline risk of cardiovascular events.

Conclusions: Based on current pricing and willingness-to-pay thresholds, most CEA studies considered ezetimibe, n-3 PUFAs and the polypill to be cost effective compared with standard care but not PCSK9 inhibitors for secondary prevention of CVD.
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http://dx.doi.org/10.1007/s40273-020-00936-0DOI Listing
October 2020

Vitamin D-Binding Protein in Pregnancy and Reproductive Health.

Nutrients 2020 May 20;12(5). Epub 2020 May 20.

Monash Centre for Health Research and Implementation (MCHRI) and Centre of Cardiovascular Research and Education in Therapeutics (CCRET), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168 VIC, Australia.

Vitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships.
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http://dx.doi.org/10.3390/nu12051489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285222PMC
May 2020

Histidine-containing dipeptides reduce central obesity and improve glycaemic outcomes: A systematic review and meta-analysis of randomized controlled trials.

Obes Rev 2020 03 11;21(3):e12975. Epub 2019 Dec 11.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Supplementation with histidine-containing dipeptides has been shown to improve obesity and glycaemic outcomes in animal and human studies. We conducted a systematic review and meta-analysis of randomized controlled trials to examine these effects. Electronic databases were searched investigating the effects of histidine-containing dipeptides supplementation on anthropometric and glycaemic outcomes. Meta-analyses were performed using random-effects models to calculate the weighted mean difference and 95% confidence interval. There were 30 studies for the systematic review and 23 studies pooled for meta-analysis. Histidine-containing dipeptide groups had a lower waist circumference (WMD [95% CI] = -3.53 cm [-5.65, -1.41], p = 0.001) and HbA1c level (WMD [95% CI] = -0.76% (8.5 mmol/mol) [-1.29% (14.3 mmol/mol), -0.24% (2.8 mmol/mol)], p = 0.004) at follow-up compared with controls. In sensitivity analyses of studies with low risk of bias, waist circumference, HbA1c, and fasting glucose levels (WMD [95% CI] = -0.63 mmol/L [-1.09, -0.18], p = 0.006) were significantly lower in intervention groups versus controls. There was also a trend toward lower fat mass (p = 0.09), insulin resistance (p = 0.07), and higher insulin secretion (p = 0.06) in intervention versus control groups. Supplementation with histidine-containing dipeptides may reduce central obesity and improve glycaemic outcomes. Further studies exploring histidine-containing dipeptide use in obesity and diabetes prevention and treatment are warranted.
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http://dx.doi.org/10.1111/obr.12975DOI Listing
March 2020

Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells.

Eur J Pharm Biopharm 2019 Dec 16;145:65-75. Epub 2019 Oct 16.

Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. Electronic address:

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.
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http://dx.doi.org/10.1016/j.ejpb.2019.10.004DOI Listing
December 2019

Increased Inflammation and Cardiometabolic Risk in Individuals with Low Copy Numbers.

J Clin Med 2019 Mar 19;8(3). Epub 2019 Mar 19.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia.

Lower copy number variations (CNVs) in the salivary amylase gene () have been associated with obesity and insulin resistance; however, the relationship between and cardiometabolic risk has not been fully elucidated. Using gold-standard measures, we aimed to examine whether CNVs are associated with cardiometabolic risk factors in an overweight or obese, otherwise healthy population. Fifty-seven adults (58% male) aged 31.17 ± 8.44 years with a body mass index (BMI) ≥25 kg/m² were included in the study. We measured CNVs (qPCR); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, serum lipids by ELISA); insulin sensitivity (hyperinsulinaemic⁻euglycaemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (multiplex assays). Based on previous studies and median values, participants were divided into low (≤4) and high (>4) CNV groups. Low carriers ( = 29) had a higher fat mass (40.76 ± 12.11 versus 33.33 ± 8.50 kg, = 0.009) and LDL-cholesterol (3.27 ± 0.80 versus 2.87 ± 0.69 mmol/L, = 0.038), and higher serum levels of interleukin [IL]-6, IL-1β, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1) (all < 0.05) compared with high carriers ( = 28), but there were no differences in glycaemic measures, including insulin sensitivity or secretion (all > 0.1). Except for MCP-1, the results remained significant in multivariable models adjusted for age, sex, and fat mass (all < 0.05). Our findings suggest that low CNVs are associated with increased cardiovascular disease risk and inflammation, but not glucose metabolism, in overweight or obese adults.
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http://dx.doi.org/10.3390/jcm8030382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463254PMC
March 2019

The relevance of Brownian relaxation as power absorption mechanism in Magnetic Hyperthermia.

Sci Rep 2019 03 8;9(1):3992. Epub 2019 Mar 8.

Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, C/Mariano Esquillor s/n, CP 50018, Zaragoza, Spain.

The Linear Response Theory (LRT) is a widely accepted framework to analyze the power absorption of magnetic nanoparticles for magnetic fluid hyperthermia. Its validity is restricted to low applied fields and/or to highly anisotropic magnetic nanoparticles. Here, we present a systematic experimental analysis and numerical calculations of the specific power absorption for highly anisotropic cobalt ferrite (CoFeO) magnetic nanoparticles with different average sizes and in different viscous media. The predominance of Brownian relaxation as the origin of the magnetic losses in these particles is established, and the changes of the Specific Power Absorption (SPA) with the viscosity of the carrier liquid are consistent with the LRT approximation. The impact of viscosity on SPA is relevant for the design of MNPs to heat the intracellular medium during in vitro and in vivo experiments. The combined numerical and experimental analyses presented here shed light on the underlying mechanisms that make highly anisotropic MNPs unsuitable for magnetic hyperthermia.
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http://dx.doi.org/10.1038/s41598-019-40341-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408542PMC
March 2019

Magneto-plasmonic nanoparticles as theranostic platforms for magnetic resonance imaging, drug delivery and NIR hyperthermia applications.

Nanoscale 2014 Aug;6(15):9230-40

Department of Chemical Engineering, Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Río Ebro-Edificio I+D, C/Poeta Mariano Esquillor S/N, 50018-Zaragoza, Spain.

PEGylated magneto-plasmonic nanoparticles with a hollow or semi-hollow interior have been successfully synthesized and their physico-chemical characteristics have been investigated. The hollow interior space can be used to store drugs or other molecules of interest whereas magnetic characterization shows their potential as contrast agents in magnetic resonance imaging (MRI) applications. In addition, their plasmonic characteristics in the near infrared (NIR) region make them efficient in photothermal applications producing high temperature gradients after short irradiation times. We show that by controlling the etching conditions the inner silica shell can be selectively dissolved to achieve a hollow or semi-hollow interior without compromising the magnetic or plasmonic characteristics of the resulting nanoparticles. Magnetic measurements and transmission electron microscopy observations have been used to demonstrate the precise control during the etching process and to select an optimal concentration of the etching reagent and contact time to preserve the inner superparamagnetic iron oxide-based nanoparticles and the plasmonic properties of the constructs. Drug loading capabilities were also evaluated for both semi-hollow and as-synthesized nanoparticles using Rhodamine B isothiocyanate as a model compound. The nanoparticles produced could be potentially used as "theranostic" nanoparticles with both imaging capabilities and a dual therapeutic function (drug delivery and hyperthermia).
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http://dx.doi.org/10.1039/c4nr01588fDOI Listing
August 2014

Quantum dot and superparamagnetic nanoparticle interaction with pathogenic fungi: internalization and toxicity profile.

ACS Appl Mater Interfaces 2014 Jun 5;6(12):9100-10. Epub 2014 Jun 5.

Instituto de Agricultura Sostenible, CSIC , Alameda del Obispo s/n, Córdoba, Spain.

For several years now, nanoscaled materials have been implemented in biotechnological applications related to animal (in particular human) cells and related pathologies. However, the use of nanomaterials in plant biology is far less widespread, although their application in this field could lead to the future development of plant biotechnology applications. For any practical use, it is crucial to elucidate the relationship between the nanomaterials and the target cells. In this work we have evaluated the behavior of two types of nanomaterials, quantum dots and superparamagnetic nanoparticles, on Fusarium oxysporum, a fungal species that infects an enormous range of crops causing important economic losses and is also an opportunistic human pathogen. Our results indicated that both nanomaterials rapidly interacted with the fungal hypha labeling the presence of the pathogenic fungus, although they showed differential behavior with respect to internalization. Thus, whereas magnetic nanoparticles appeared to be on the cell surface, quantum dots were significantly taken up by the fungal hyphae showing their potential for the development of novel control approaches of F. oxysporum and related pathogenic fungi following appropriate functionalization. In addition, the fungal germination and growth, accumulation of ROS, indicative of cell stress, and fungal viability have been evaluated at different nanomaterial concentrations showing the low toxicity of both types of nanomaterials to the fungus. This work represents the first study on the behavior of quantum dots and superparamagnetic particles on fungal cells, and constitutes the first and essential step to address the feasibility of new nanotechnology-based systems for early detection and eventual control of pathogenic fungi.
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http://dx.doi.org/10.1021/am501029gDOI Listing
June 2014

Influence of a silica interlayer on the structural and magnetic properties of sol-gel TiO₂-coated magnetic nanoparticles.

Langmuir 2014 May 28;30(18):5238-47. Epub 2014 Apr 28.

Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza , Mariano Esquillor s/n, 50018 Zaragoza, Spain.

Superparamagnetic iron oxide nanoparticles coated with titanium dioxide have been synthesized, growing the titanium dioxide directly either on the magnetic nuclei or on magnetic nanoparticles previously coated with a semihydrophobic silica layer. Both coatings have been obtained by sol-gel. Since it is well-known that the existence of the intermediate silica layer influences the physicochemical properties of the material, a detailed characterization of both types of coatings has been carried out. The morphology, structure, and composition of the synthesized nanomatrices have been locally analyzed with subangstrom spatial resolution, by means of aberration corrected transmission electron microscopy (HRTEM and STEM-HAADF). Besides magnetization measurements, proton relaxivity experiments have been also performed on water suspensions of the as-synthesized nanoparticles to investigate the role of the silica interlayer in the relaxometric properties. The silica interlayer leads to nanoparticles with much higher water stability and to higher relaxivity of the suspensions.
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http://dx.doi.org/10.1021/la500423eDOI Listing
May 2014

Spatially-resolved EELS analysis of antibody distribution on biofunctionalized magnetic nanoparticles.

ACS Nano 2013 May 29;7(5):4006-13. Epub 2013 Apr 29.

Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia de Aragon, Universidad de Zaragoza, 50018 Zaragoza, Spain.

Spatially resolved electron energy loss spectroscopy (SR-EELS) using scanning transmission electron microscope (STEM) allows the identification and determination of the spatial distribution of the components/elements of immuno-functionalized core-shell superparamagnetic magnetite nanoparticles. Here, we report that SR-EELS measurements allow the direct identification and study of the biological moieties (protein G and anti-HRP antibody) in complex bionanocarriers of relevance for biomedical applications. Our findings show that the biomacromolecules are located on specific areas on the nanoparticles' surface. In addition, efficiency of this functionalization was evaluated by means of biochemical techniques.
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http://dx.doi.org/10.1021/nn306028tDOI Listing
May 2013

Synthesis, application, and tracking of magnetic carbon-coated nanoparticles in plants.

Methods Mol Biol 2012 ;906:263-72

Área de Mejora y Biotecnología, IFAPA, Centro Alameda del Obispo, Córdoba, Spain.

The behavior of nanoparticles inside plants is gaining importance for its implications in research about putative applications and toxicology. Magnetic carbon-coated nanoparticles can be easily traced through plant tissues using simple and affordable histological techniques. Here we present a methodology for the synthesis of such nanoparticles. We also describe methods for growing plants using rhizotrons (in order to observe the roots), procedures for applying the nanoparticles, taking and processing the samples.
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http://dx.doi.org/10.1007/978-1-61779-953-2_20DOI Listing
November 2012

Effect of magnet implant on iron biodistribution of Fe@C nanoparticles in the mouse.

Arch Pharm Res 2012 Jan 2;35(1):93-100. Epub 2012 Feb 2.

Departament de Farmàcia i Tecnologia Farmacèutica, Unitat de Biofarmàcia i Farmacocinètica, E-08028 Barcelona, Spain.

The in vivo biodistribution of Fe@C nanoparticles (NP) was tested in mice bearing an inflammatory focus induced by injecting carrageenan into an air pouch previously formed on their back. The animals were intravenously injected NP with a high (60 mg/kg) or a low iron dose (6 mg/kg) and sacrificed 2 h later. Blood and organ samples (liver, spleen, lung, and kidney) were obtained; washed exudates were also collected. Iron concentration in plasma, blood cells, organs, and exudates was determined by flameless atomic-absorption-spectroscopy after digestion of organic material. Pouch exudate volume increased in all groups of mice with experimental inflammation. After i.v. administration of the high and low dose of NP, iron in exudate increased by 83.3% and 92.2%, respectively. A similar increase in hepatic iron appeared after the high dose (78%), but no increase appeared after the low dose. When the magnet was present, a 157% and 119% increase of iron in exudate appeared after both doses of NPs, but only the high dose of NP increased iron liver (60%). The presence of a magnetic field in the pouch favored selective biodistribution of NP in the inflammatory focus. These results indicate that mice with an inflammatory compartment are suitable for primary screening of different NP types. They also show that selective biodistribution is greater when a low dose of NP was used and that distribution in the target organ was increased by the magnetic field.
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http://dx.doi.org/10.1007/s12272-012-0109-8DOI Listing
January 2012

Absorption and translocation to the aerial part of magnetic carbon-coated nanoparticles through the root of different crop plants.

J Nanobiotechnology 2010 Nov 8;8:26. Epub 2010 Nov 8.

IFAPA, Centro Alameda del Obispo, Área de Mejora y Biotecnología, Avda, Menédez Pidal s/n, PO Box 3092, Córdoba, 14004 Spain.

The development of nanodevices for agriculture and plant research will allow several new applications, ranging from treatments with agrochemicals to delivery of nucleic acids for genetic transformation. But a long way for research is still in front of us until such nanodevices could be widely used. Their behaviour inside the plants is not yet well known and the putative toxic effects for both, the plants directly exposed and/or the animals and humans, if the nanodevices reach the food chain, remain uncertain. In this work we show that magnetic carbon-coated nanoparticles forming a biocompatible magnetic fluid (bioferrofluid) can easily penetrate through the root in four different crop plants (pea, sunflower, tomato and wheat). They reach the vascular cylinder, move using the transpiration stream in the xylem vessels and spread through the aerial part of the plants in less than 24 hours. Accumulation of nanoparticles was detected in wheat leaf trichomes, suggesting a way for excretion/detoxification. This kind of studies is of great interest in order to unveil the movement and accumulation of nanoparticles in plant tissues for assessing further applications in the field or laboratory.
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http://dx.doi.org/10.1186/1477-3155-8-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994779PMC
November 2010

Nanoparticle penetration and transport in living pumpkin plants: in situ subcellular identification.

BMC Plant Biol 2009 Apr 23;9:45. Epub 2009 Apr 23.

Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, E-28040, Madrid, Spain.

Background: In recent years, the application of nanotechnology in several fields of bioscience and biomedicine has been studied. The use of nanoparticles for the targeted delivery of substances has been given special attention and is of particular interest in the treatment of plant diseases. In this work both the penetration and the movement of iron-carbon nanoparticles in plant cells have been analyzed in living plants of Cucurbita pepo.

Results: The nanoparticles were applied in planta using two different application methods, injection and spraying, and magnets were used to retain the particles in movement in specific areas of the plant. The main experimental approach, using correlative light and electron microscopy provided evidence of intracellular localization of nanoparticles and their displacement from the application point. Long range movement of the particles through the plant body was also detected, particles having been found near the magnets used to immobilize and concentrate them. Furthermore, cell response to the nanoparticle presence was detected.

Conclusion: Nanoparticles were capable of penetrating living plant tissues and migrating to different regions of the plant, although movements over short distances seemed to be favoured. These findings show that the use of carbon coated magnetic particles for directed delivery of substances into plant cells is a feasible application.
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http://dx.doi.org/10.1186/1471-2229-9-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680855PMC
April 2009

[Research study on renal targeted chemotherapy with magnetic harpoons and intravenous administration of ferro-carbon nanoparticles].

Arch Esp Urol 2007 Jan-Feb;60(1):5-14

Instituto Universitario de Investigación en Nanociencia de Aragón, Universidad de Zaragoza, Zaragoza.

Objectives: The use of nanoparticules for drug transport is one of the topics with priority interest within the field of biomedical research. Our objective is to show the initial results of an innovative method to focalize drug carrier ferro-carbon nanoparticules to solid organs. We obtained and characterized various types of ferrous magnetic nanoparticules and studied their behaviour in vitro and in vivo in laboratory animals with intrarenal magnetic targets laparoscopically implanted.

Methods: Using a plasma arch we obtained ferro-carbon nanoparticules with the ability to absorb and deliver doxorubicin, showing an excellent behaviour in in vitro rheological studies. Under general anesthesia and control we inserted a gold covered magnetic microharpoon in the left kidney of New Zealand rabbits. At the same time we injected intravenously different doses of various types of nanoparticules. The animals were sacrified ofter pre-established times and pathologic studies of their kidneys, spleens, livers, lungs and bone marrow were carried out.

Results: After selection of the most adequafe nanoparticules for our purposes, we ascertained significant differences in the distribution of nanoparticules in postmortem studies, with accumulation in the magnetic target and surrounding renal parenchyma. Nevertheless, the reticuloendothelial system retains a great amount of the injected dose.

Conclusions: Although our magnetic focalization system is effective, nanoparticule temporary protection systems should be tested to allow us avoid the action of the immune system.
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June 2007