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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

Nanotechnological devices for therapeutic applications are massively addressed to diseases prevalent in the developed world, particularly cancer, because of the wrong assumption (for both ethical and technical reasons) that nanomedicines are too expensive and thus they can not be applied to diseases of poverty. Here we have applied quantum dots to study at the cellular level the delivery of the contents of liposomes to erythrocytes infected by the malaria parasite Plasmodium falciparum, and to macrophages infected by the leishmaniasis causative agent Leishmania infantum. A number of works have reported on the encapsulation in liposomes of drugs against both diseases as a strategy to increase therapeutic efficacy and decrease unspecific toxicity. Liposome-carried drugs end up inside Plasmodium-infected red blood cells (pRBCs) and in the phagolysosome system of Leishmania-infected macrophages but some knowledge gaps still obscure subcellular events related to these processes. As a proof of concept, we have used confocal fluorescence microscopy to follow the fate in pRBCs and infected macrophages of quantum dots encapsulated in liposomes, and of lysosomes, leishmaniasis and malaria parasites, nuclei, and phagosomes. Our data indicate that liposomes merge their lipid bilayers with pRBC plasma membranes but are engulfed by macrophages, where they fuse with lysosomes. Lysosomes have not been observed to join with phagosomes harboring single Leishmania parasites, whereas in phagosomes where the parasite has divided there is lysosome-specific fluorescence with a concomitant disappearance of lysosomes from the cytosol. In later stages, all the lysosome-specific label is found inside phagosomes whereas the phagosomal marker cadaverine strongly stains the macrophage nucleus, suggesting that Leishmania infection induces in its later stages nuclear degeneration and, possibly, apoptosis of the host cell. These results indicate that induction of macrophage apoptosis should be explored as a possible strategy used by Leishmania to prepare its egress.

Keywords: Leishmania infantum, Leishmaniasis Liposomes, Malaria, Nanomedicine, Nanotechnology, Plasmodium falciparum, Quantum dots


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. 4th International Conference on Nanotechnology: Fundamentals and Applications , International ASET Inc. (Ontario, Canada) , 1-8

Nanotechnological devices for therapeutic applications are massively addressed to diseases prevalent in the developed world, particularly cancer, because of the wrong assumption (for both ethical and technical reasons) that nanomedicines are too expensive and thus they can not be applied to diseases of poverty. Here we have applied quantum dots to study at the cellular level the delivery of the contents of immunoliposomes to erythrocytes infected by the malaria parasite Plasmodium falciparum, and to macrophages infected by the leishmaniasis causative agent Leishmania infantum. A number of works have reported on the encapsulation in liposomes of drugs against both diseases as a strategy to increase therapeutic efficacy and decrease unspecific toxicity. Liposome-carried drugs end up inside Plasmodium-infected red blood cells (pRBCs) and in the phagolysosome system of Leishmania-infected macrophages but some knowledge gaps still obscure subcellular events related to these processes. As a proof of concept, we have used confocal fluorescence microscopy to follow the fate in pRBCs and L. infantum-infected macrophages of quantum dots encapsulated in liposomes, and of lysosomes, Leishmania and Plasmodium parasites, nuclei, and phagosomes. Our data indicate that liposomes merge their lipid bilayers with pRBC plasma membranes but are engulfed by macrophages, where they fuse with lysosomes. Lysosomes have not been observed to join with phagosomes harboring single L. infantum parasites, whereas in phagosomes where the parasite has divided there is lysosome-specific fluorescence with a concomitant disappearance of lysosomes from the cytosol. In later stages, all the lysosome-specific label is found inside phagosomes whereas the phagosomal marker cadaverine strongly stains the macrophage nucleus, suggesting that L. infantum infection induces in its later stages nuclear degeneration and possibly, apoptosis of the host cell. These results indicate that induction of macrophage apoptosis should be explored as a possible strategy used by L. infantum to prepare its egress.

Keywords: Leishmania infantum, Leishmaniasis, Liposomes, Malaria, Nanomedicine, Nanotechnology, Plasmodium falciparum, Quantum dots