Nanomalaria


The Nanomalaria group is a joint unit affiliated with IBEC and the Barcelona Institute for Global Health (ISGlobal), located in the Esther Koplowitz Centre near Hospital Clínic (Barcelona).


Xavier Fernàndez-Busquets | Group Leader
Livia Neves Borgheti Cardoso | Postdoctoral Researcher
Ernest Moles Meler | Postdoctoral Researcher
Arnau Biosca Romanillos | PhD Student
Elena Lantero Escolar | PhD Student
Laura Carol Perdiguer | Research Assistant
Alexandros Belavilas-Trovas | Masters Student

About


The current activity of the Nanomalaria group is focused on the development of nanomedicine-based systems to be applied to malaria prophylaxis, diagnosis and therapy.

Cryo-transmission electron microscope image of liposomes being assayed for the encapsulation of drugs specifically targeted to red blood cells infected by the malaria parasite Plasmodium falciparum. CryoTEM image artistic editing by Marc Cirera, www.marccirera.com.

Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium spp. The clinical, social and economic burden of malaria has led for the last 100 years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial drugs exclusively to Plasmodium-infected cells. Nanotechnology can also be applied to the discovery of new antimalarials through single-molecule manipulation approaches for the identification of novel drugs targeting essential molecular components of the parasite. Finally, methods for the diagnosis of malaria can benefit from nanotools applied to the design of microfluidic-based devices for the accurate identification of the parasite’s strain, its precise infective load, and the relative content of the different stages of its life cycle, whose knowledge is essential for the administration of adequate therapies. The benefits and drawbacks of these nanosystems have to be considered in different possible scenarios, including economy-related issues that are hampering the progress of nanotechnology-based medicines against malaria with the dubious argument that they are too expensive to be used in developing areas. Unfortunately, it is true that the application of nanoscience to infectious disease has been traditionally neglected, with most research resources overwhelmingly biased towards other pathologies more prominent in the developed world. Thus, extra ingenuity is demanded from us: malaria-oriented nanomedicines not only need to work spotlessly, they have to do so in a cost-efficient way because they will be deployed in low-income regions.

Left: Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells.

The driving force of the Nanomalaria group is our personal commitment to applying nanomedicine to infectious diseases of poverty though several research lines: (i) Exploration of different types of encapsulating structure (liposomes, synthetic and natural polymers), targeting molecule (protein, polysaccharide, nucleic acid), and antimalarial compound (e.g. new structures derived from marine organisms and antimicrobial peptides) for the assembly of nanovectors capable of delivering their drug cargo with complete specificity to diseased cells. (ii) Study of metabolic pathways present in Plasmodium but absent in humans, with the aim of identifying specific enzymes as therapeutic targets. (iii) Use of glycosaminoglycans for innovative antimalarial strategies. (iv) Design of new methods for the targeted drug delivery to Plasmodium stages in the mosquito vector. (v) Investigation of novel drugs against insect-borne diseases working through radically new mechanisms. (vi) Extension of our activities to new pathologies (leishmaniasis).

News/Jobs

Liposomes image is Pinacoteca winner for April
30/03/17

An image from Xavier Fernandez-Busquets’ Nanomalaria joint unit has been selected as Image of the Month for April 2017 for the Pinacoteca de la Ciencia, a competition run by the Spanish Society for Biochemistry and Molecular Biology (SEBBM).


Drug-loaded nanovectors covered with antibodies represent an innovative approach to combat malaria
13/10/16

A study led by Xavier Fernández Busquets, director of the joint ISGlobal-IBEC Nanomalaria unit, describes an innovative approach to selectively eliminate red blood cells infected by Plasmodium falciparum, avoid their aggregation, and inhibit parasite growth.


New strategies to combat malaria: heparin and nanomedicine
28/09/16

The Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute for Global Health (ISGlobal) and the biotech firm Bioiberica have signed a partnership agreement to study the development of new compounds derived from heparin to combat malaria.


Looking to the ocean for malaria solutions
17/05/16

Researchers have found heparin-like molecules with reduced blood-thinning activity that can be used for therapeutic approaches against malaria – in sea cucumbers, red algae and marine sponges.


New malaria strategy proposes using unaffected red blood cells as drug carriers
12/06/15

IBEC and ISGlobal’s joint unit, Nanomalaria, has published a new therapeutic strategy against malaria.


Heparin exhibits dual activity against malaria
07/07/14

A study by researchers from IBEC, ISGlobal and the University of Barcelona published in Nanomedicine opens the door to improved treatment of malaria with heparin.


IBEC and Israeli Ministry of Health join forces to promote nanomedicine
04/07/14

IBEC’s Xavier Fernández-Busquets appears in a video produced by the EU-funded ERA-NET project EuroNanoMed on “Drug Delivery: The Use of Nanoparticles in Medicine”.


Nanoparticles as drug carriers for malaria
27/02/14

A study by researchers from the Institute for Bioengineering of Catalonia (IBEC) and the Barcelona Centre for International Health Research (CRESIB) demonstrates that an antimalarial drug encapsulated in nanoparticles—chloroquine salts in polyamidoamine polymers—is significantly more effective when delivered in vivo than free (unencapsulated) drugs and may help to curb drug resistance.


“Nanorobots de disseny per atacar la malària”
18/11/2013

IBEC Director and Head of Nanobioengineering, Josep Samitier, and the head of the joint IBEC/CRESIB unit on Nanomalaria, Xavier Fernández-Busquets, both featured in an article in the Catalan daily newspaper Ara this weekend.


A promising strategy to target malaria
20/12/2012

A paper by the Nanobioengineering group reveals a new strategy for targeted malaria treatment that doesn’t rely on the use of expensive antibodies.

Projects

National projects
Amphoteric polyamidoamines as innovative tools to selectively direct antimalarial drugs towards Plasmodium-infected red blood cells Fundación CARIPLO Xavier Fernández- Busquets
NANOMALNET Exploración de nuevas moléculas direccionadoras eficientes para la liberación de antimaláricos Biotechnology Programme, MINECO, Spain (BIO2011-25039) Xavier Fernández-Busquets
NANOMISSION Ingeniería de nanovectores para la liberación de fármacos antimaláricos a fases de transmisión de Plasmodium MINECO, Retos investigación: Proyectos I+D Xavier Fernández- Busquets
Privately-funded projects
Identificació de fraccions d’heparina com a noves teràpies antimalàriques Bioiberica, S.A. Xavier Fernández- Busquets

Publications

Marques, J., Valle-Delgado, J. J., Urbán, P., Baró, E., Prohens, R., Mayor, A., Cisteró, P., Delves, M., Sinden, R. E., Grandfils, C., de Paz, J. L., García-Salcedo, J. A., Fernàndez-Busquets, X., (2017). Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery Nanomedicine: Nanotechnology, Biology, and Medicine 13, 2, 515-525

Caddeo, C., Manca, M. L., Matos, M., Gutierrez, G., Díez-Sales, O., Peris, J. E., Usach, I., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2017). Functional response of novel bioprotective poloxamer-structured vesicles on inflamed skin Nanomedicine: Nanotechnology, Biology, and Medicine 13, 3, 1127-1136

Caddeo, C., Pons, R., Carbone, C., Fernàndez-Busquets, X., Cardia, M. C., Maccioni, A. M., Fadda, A. M., Manconi, M., (2017). Physico-chemical characterization of succinyl chitosan-stabilized liposomes for the oral co-delivery of quercetin and resveratrol Carbohydrate Polymers 157, 1853-1861

Moles, E., Marcos, J., Imperial, S., Pozo, O. J., Fernàndez-Busquets, X., (2017). 2-picolylamine derivatization for high sensitivity detection of abscisic acid in apicomplexan blood-infecting parasites Talanta 168, 130-135

Vitonyte, J., Manca, M. L., Caddeo, C., Valenti, D., Peris, J. E., Usach, I., Nacher, A., Matos, M., Gutiérrez, G., Orrù, G., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2017). Bifunctional viscous nanovesicles co-loaded with resveratrol and gallic acid for skin protection against microbial and oxidative injuries European Journal of Pharmaceutics and Biopharmaceutics 114, 278-287

Moles, E., Moll, K., Ch'ng, J. H., Parini, P., Wahlgren, M., Fernàndez-Busquets, X., (2016). Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells Journal of Controlled Release 241, 57-67

Guivernau, B., Bonet, J., Valls-Comamala, V., Bosch-Morató, M., Godoy, J. A., Inestrosa, N. C., Perálvarez-Marín, A., Fernàndez-Busquets, X., Andreu, D., Oliva, B., Muñoz, F. J., (2016). Amyloid- Journal of Neuroscience 36, 46, 11693-11703

Marques, J., Vilanova, Eduardo, Mourão, Paulo A. S., Fernàndez-Busquets, Xavier, (2016). Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium Scientific Reports 6, 24368 [Open Access]

Ch'ng, Jun-Hong, Moll, Kirsten, Quintana, Maria del Pilar, Chan, Sherwin Chun Leung, Masters, Ellen, Moles, Ernest, Liu, Jianping, Eriksson, Anders B., Wahlgren, Mats, (2016). Rosette-disrupting effect of an anti-plasmodial compound for the potential treatment of plasmodium falciparum malaria complications Scientific Reports 6, 29317

Fernàndez-Busquets, X., (2016). Novel strategies for Plasmodium-targeted drug delivery Expert Opinion on Drug Delivery 13, 7, 919-922

Vilanova, Eduardo, Santos, Gustavo R. C., Aquino, Rafael S., Valle-Delgado, Juan J., Anselmetti, Dario, Fernàndez-Busquets, Xavier, Mourão, Paulo A. S., (2016). Carbohydrate-carbohydrate interactions mediated by sulfate esters and calcium provide the cell adhesion required for the emergence of early metazoans Journal of Biological Chemistry 291, 18, 9425-9437

Caddeo, C., Nacher, A., Vassallo, A., Armentano, M. F., Pons, R., Fernàndez-Busquets, X., Carbone, C., Valenti, D., Fadda, A. M., Manconi, M., (2016). Effect of quercetin and resveratrol co-incorporated in liposomes against inflammatory/oxidative response associated with skin cancer International Journal of Pharmaceutics 513, 1-2, 153-163

Credi, C., De Marco, C., Molena, E., Pla Roca, M., Samitier, J., Marques, J., Fernàndez-Busquets, X., Levi, M., Turri, S., (2016). Heparin micropatterning onto fouling-release perfluoropolyether-based polymers via photobiotin activation Colloids and Surfaces B: Biointerfaces 146, 250-259

Valle-Delgado, J. J., Fernàndez-Busquets, X., (2016). Rapid diagnostic tests for malaria: Past, present and future Future Microbiology 11, 11, 1379-1382

Moles, Ernest, Valle-Delgado, Juan José, Urbán, Patricia, Azcárate, Isabel G., Bautista, José M., Selva, Javier, Egea, Gustavo, Ventura, Salvador, Fernàndez-Busquets, Xavier, (2015). Possible roles of amyloids in malaria pathophysiology Future Science OA 1, 2, FSO43

Manca, M. L., Castangia, I., Zaru, M., Nácher, A., Valenti, D., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2015). Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring Biomaterials 71, 100-109

Moles, E., Urbán, P., Jiménez-Díaz, M. B., Viera-Morilla, S., Angulo-Barturen, I., Busquets, M. A., Fernàndez-Busquets, X., (2015). Immunoliposome-mediated drug delivery to Plasmodium-infected and non-infected red blood cells as a dual therapeutic/prophylactic antimalarial strategy Journal of Controlled Release 210, 217-229

Castangia, I., Nácher, A., Caddeo, C., Merino, V., Díez-Sales, O., Catalán-Latorre, A., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2015). Therapeutic efficacy of quercetin enzyme-responsive nanovesicles for the treatment of experimental colitis in rats Acta Biomaterialia 13, 216-227

Urbán, Patricia, Ranucci, Elisabetta, Fernàndez-Busquets, Xavier, (2015). Polyamidoamine nanoparticles as nanocarriers for the drug delivery to malaria parasite stages in the mosquito vector Nanomedicine 10, 22, 3401-3414

Moles, E., Fernàndez-Busquets, X., (2015). Loading antimalarial drugs into noninfected red blood cells: An undesirable roommate for Plasmodium Future Medicinal Chemistry 7, 7, 837-840

Castangia, I., Manca, M. L., Matricardi, P., Catalán-Latorre, A., Nácher, A., Diez-Sales, O., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2015). Effects of ethanol and diclofenac on the organization of hydrogenated phosphatidylcholine bilayer vesicles and their ability as skin carriers Journal of Materials Science: Materials in Medicine 26, 137

Fernàndez-Busquets, X., de Groot, N.S., Ventura, S., (2015). Structural and computational insights into conformational diseases: A review Bentham Science Publishers 7, 134-182

Pujol, A., Urbán, P., Riera, C., Fisa, R., Molina, I., Salvador, F., Estelrich, J., Fernàndez-Busquets, X., (2014). Application of quantum dots to the study of liposome targeting in leishmaniasis and malaria International Journal of Theoretical and Applied Nanotechnology 2, 1, 1-8

Fernàndez-Busquets, X., (2014). Toy kit against malaria: Magic bullets, LEGO, Trojan horses and Russian dolls Therapeutic Delivery 5, 10, 1049-1052

Movellan, J., Urbán, P., Moles, E., de la Fuente, J. M., Sierra, T., Serrano, J. L., Fernàndez-Busquets, X., (2014). Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs Biomaterials 35, 27, 7940-7950

Urbán, P., Valle-Delgado, J. J., Mauro, N., Marques, J., Manfredi, A., Rottmann, M., Ranucci, E., Ferruti, P., Fernàndez-Busquets, X., (2014). Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Journal of Controlled Release 177, 1, 84-95

Marques, J., Moles, E., Urbán, P., Prohens, R., Busquets, M. A., Sevrin, C., Grandfils, C., Fernàndez-Busquets, X., (2014). Application of heparin as a dual agent with antimalarial and liposome targeting activities toward Plasmodium-infected red blood cells Nanomedicine: Nanotechnology, Biology, and Medicine 10, 8, 1719-1728

Paaijmans, Krijn, Fernàndez-Busquets, Xavier, (2014). Antimalarial drug delivery to the mosquito: an option worth exploring? Future Microbiology 9, 5, 579-582

Manca, M. L., Castangia, I., Matricardi, P., Lampis, S., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2014). Molecular arrangements and interconnected bilayer formation induced by alcohol or polyalcohol in phospholipid vesicles Colloids and Surfaces B: Biointerfaces 117, 360-367

Ramos-Fernández, E., Tajes, M., Palomer, E., Ill-Raga, G., Bosch-Morató, M., Guivernau, B., Román-Dégano, I., Eraso-Pichot, A., Alcolea, D., Fortea, J., Nuñez, L., Paez, A., Alameda, F., Fernàndez-Busquets, X., Lleó, A., Elosúa, R., Boada, M., Valverde, M. A., Muñoz, F. J., (2014). Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: Implications in cytotoxicity and amyloid- Journal of Alzheimer's Disease 40, 3, 643-657

Urbán, P., Fernàndez-Busquets, X., (2014). Nanomedicine against malaria Current Medicinal Chemistry 21, 5, 605-629

Caddeo, C., Díez-Sales, O., Pons, R., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2014). Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: In vivo and in vitro evaluation Pharmaceutical Research 31, 4, 959-968

Le Roux, D., Burger, P. B., Niemand, J., Grobler, A., Urbán, P., Fernàndez-Busquets, X., Barker, R. H., Serrano, A. E., I. Louw, A., Birkholtz, L. M., (2014). Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic International Journal for Parasitology: Drugs and Drug Resistance 4, 1, 28-36

Tajes, M., Ramos-Fernández, E., Weng-Jiang, X., Bosch-Morató, M., Guivernau, B., Eraso-Pichot, A., Salvador, B., Fernàndez-Busquets, X., Roquer, J., Muñoz, F. J., (2014). The blood-brain barrier: Structure, function and therapeutic approaches to cross it Molecular Membrane Biology 31, 5, 152-167

Valle-Delgado, J. J., Urbán, P., Fernàndez-Busquets, X., (2013). Demonstration of specific binding of heparin to Plasmodium falciparum-infected vs. non-infected red blood cells by single-molecule force spectroscopy Nanoscale 5, 9, 3673-3680

Fernàndez-Busquets, X., (2013). Amyloid fibrils in neurodegenerative diseases: villains or heroes? Future Medicinal Chemistry 5, 16, 1903-1906

Fernàndez-Busquets, X., (2013). Heparin-functionalized nanocapsules: Enabling targeted delivery of antimalarial drugs Future Medicinal Chemistry 5, 7, 737-739

Castangia, I., Manca, M. L., Matricardi, P., Sinico, C., Lampis, S., Fernàndez-Busquets, X., Fadda, A. M., Manconi, M., (2013). Effect of diclofenac and glycol intercalation on structural assembly of phospholipid lamellar vesicles International Journal of Pharmaceutics 456, 1, 1-9

Pujol, A., Riera, C., Fisa, R., Molina, I., Salvador, F., Estelrich, J., Urbán, P., Fernàndez-Busquets, X., (2013). Nanomedicine for infectious diseases: Application of quantum dots encapsulated in immunoliposomes to the study of targeted drug delivery against leishmaniasis and malaria Proceedings of the 4th International Conference on Nanotechnology: Fundamentals and Applications. International ASET Inc. , 1-8

Equipment

  • Zeiss Primostar microscope
  • Shake ‘N’ Stack (Thermo Hybaid) hybridization oven
  • Rotatory evaporator RS 3000-V (Selecta)
  • Plasmodium falciparum cell cultures

Collaborations

  • Prof. Dario Anselmetti
    Universität Bielefeld, Germany
  • Prof. Maria Antònia Busquets
    University of Barcelona, Spain
  • Prof. Elisabetta Ranucci
    Università degli Studi di Milano, Italy
  • Prof. José Manuel Bautista
    Universidad Complutense de Madrid, Spain
  • Dr. Matthias Rottmann
    Swiss Tropical and Public Health Institute, Basel, Switzerland
  • Prof. Robert Sinden
    Imperial College London, UK
  • Dr. Israel Molina
    Hospital Universitari Vall d’Hebron, Barcelona
  • Prof. José Luis Serrano
    Instituto de Nanociencia de Aragón, Zaragoza
  • Prof. Johan Engbersen
    University of Twente, The Netherlands
  • Dr. Santiago Imperial
    University of Barcelona, Spain
  • Dr. Eduardo Prata Vilanova
    Universidade Federal do Rio de Janeiro, Brazil
  • Dr. Maria Manconi
    Università de Cagliari, Sardinia, Italy
  • Dr. Krijn Paaijmans
    CRESIB, Barcelona, Spain
  • Dr. Ellen Faszewski
    Wheelock College, Boston, USA
  • Prof. Bernard Degnan
    University of Brisbane, Australia
  • Dr. Francisco J. Muñoz
    Parc de Recerca Biomèdica de Barcelona, Spain
  • Prof. Salvador Ventura
    Universitat Autònoma de Barcelona, Bellaterra, Spain
  • Dr. Juan José Valle-Delgado
    Aalto University, Helsinki, Finland
  • Prof. Mats Wahlgren
    Karolinska Institutet, Stockholm, Sweden
  • Dr. Fatima Nogueira
    Instituto de Higiene e Medicina Tropical, Lisboa, Portugal
  • Dr. Christian Grandfils
    University of Liège, Belgium

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