Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark

Montanari, Jorge; Maidana, Cristina Graciela; Esteva, M; Salomón, Claudio J.; Morilla, María José; Romero, Eder Lilia

doi:10.1016/j.jconrel.2010.08.014

Cited by 60 publications

(51 citation statements)

References 56 publications

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“…Interestingly, this was achieved at a 100-fold lower dose of PS (1.25 µM) and 75-fold lower fluency (15 J/cm 2 ) than we have reported before with ZnPcUDLs ([tetrakis{2,4-dimetil-3-pentyloxi}-phthalocyaninate] zinc [II]). 35 On the other hand, our results were achieved at 10 4 -10 5 -fold lower doses of PS (1 mM δ-aminolevulinic acid [ALA] and 1 mM PpIX) and 50-100-fold lower fluency (50-10 J/cm 2 ) than with ALA or PpIX, that had previously failed to eliminate intracellular L. major amastigotes. 54,55 With such an approach, macrophages were more sensitive than the parasites to ALA, suggesting that death of the host cells likely occurred without complete eradication of the parasites.…”

Section: Znpc Concentration (µM) Ros Production (%)mentioning

confidence: 69%

“…With the idea of a further topical treatment, we had already shown that in vitro activity of a hydrophobic ZnPc ([tetrakis{2, 4- 35 In particular, these liposomes increased from 20% to 100% the antipromastigote activity and from 30% to 60% the antiamastigote activity (AA) of ZnPc, independently of irradiation. The increased AA of these UDLs was presumably due to their phagocytic uptake by the infected host cells.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Perez

Casasco

Schilrreff

et al. 2014

IJN

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In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and −35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 µM ZnPc and 7.6 µM phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm 2 ) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin-and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes.

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Section: Znpc Concentration (µM) Ros Production (%)mentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Perez

Casasco

Schilrreff

et al. 2014

IJN

Self Cite

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“…Anti-Leishmania PDT has been assessed experimentally in vivo in different animal models of CL and in vitro in infected macrophages. More recent work includes the use of different photosensitizers, e.g., hypericin, phthalocyanines, phenothiazines, methylene blue, and zinc oxide, as such or after PEGylation or in liposome-/nanoparticle-encapsulated forms, to generate ROS by illumination using different light sources, e.g., light-emitting diodes (LED), lasers, and sunlight (9)(10)(11)(12)(13)(14)(15)(16)(17). The intrinsic susceptibilities of both stages of Leishmania, i.e., promastigotes and amastigotes, to PDT has been examined in that context but rarely has been explored at the cellular and molecular levels.…”

mentioning

confidence: 99%

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Al‐Qahtani

Alkahtani

Kolli

et al. 2016

Antimicrob Agents Chemother

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dPhotodynamic inactivation of Leishmania spp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency against Leishmania tropica promastigotes and axenic amastigotes in vitro. The uptake of these PCs by both Leishmania stages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation of Leishmania spp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitized Leishmania tropica strains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ϳ650 nm) at a fluence of 1 to 2 J cm ؊2 . Quantitative fluorescence assays based on the loss of GFP/CFSE from live Leishmania tropica showed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Leishmania tropica strains are >100 times more sensitive than their host cells or macrophages to PC1-and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC 50 s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation of Leishmania spp. for use as vaccines or vaccine carriers.

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“…Our research group has shown that anti-amastigote activity of hydrophobic Zn phthalocyanine against intracellular L. braziliensis was significantly increased when loaded in ultradeformable liposomes (SoyPc: sodium cholate, 6:1 w/w) because of the increased skin penetration and uptake by infected cells of these liposomes (Montanari et al, 2010). An improved formulation containing total polar lipids (TPL) extracted from the hyperhalophile archaea Halorubrum tebenquichense that were more extensively takenup by macrophages eliminated intracellular L. braziliensis amastigotes, without reducing the viability of host cells, keratinocytes, and bone marrowÀderived dendritic cells on visible light illumination (0.2 J/cm 2 ) (Perez et al, 2014).…”

Section: Nanomedical Photodynamic Therapymentioning

confidence: 99%

Nanomedical Therapeutic and Prophylaxis Strategies Against Intracellular Protozoa in the Americas

Morilla

Romero

2015

Nanotechnology in Diagnosis, Treatment and Prophylaxis of Infectious Diseases

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Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark

Cited by 60 publications

References 56 publications

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica

Nanomedical Therapeutic and Prophylaxis Strategies Against Intracellular Protozoa in the Americas

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