Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) is an alternative to antibiotics that has potential for the treatment of chronic skin wounds, but requires improved, highly selective photosensitizer systems. Rhenium (Re)‐complex‐ and iridium (Ir)‐complex‐based phospholipid conjugates, as PDT‐functional bui...

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Main Authors: Giulia Kassab, Neha Manav, Layla Pires, Miffy H. Y. Cheng, Yulin Mo, Hilde H. Buzzá, Iti Gupta, Juan Chen, Gang Zheng
Format: Article
Language:English
Published: Wiley-VCH 2024-02-01
Series:Small Science
Subjects:
Online Access:https://doi.org/10.1002/smsc.202300131
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author Giulia Kassab
Neha Manav
Layla Pires
Miffy H. Y. Cheng
Yulin Mo
Hilde H. Buzzá
Iti Gupta
Juan Chen
Gang Zheng
author_facet Giulia Kassab
Neha Manav
Layla Pires
Miffy H. Y. Cheng
Yulin Mo
Hilde H. Buzzá
Iti Gupta
Juan Chen
Gang Zheng
author_sort Giulia Kassab
collection DOAJ
description Antimicrobial photodynamic therapy (aPDT) is an alternative to antibiotics that has potential for the treatment of chronic skin wounds, but requires improved, highly selective photosensitizer systems. Rhenium (Re)‐complex‐ and iridium (Ir)‐complex‐based phospholipid conjugates, as PDT‐functional building blocks for liposomes, are presented, and varying structural components and proportion of compounds are explored, including adjusting the cholesterol and polyethylene glycol (PEG)‐lipid contents, incorporating ethylenediaminetetraacetic acid (EDTA)‐lipid, and introducing the cationic lipid 1,2‐dioleoyl‐3‐trimethylammonium propane (DOTAP) to enhance their efficacy and selectivity in aPDT. Ir/Re‐liposomes have nanostructurally enhanced photoactivity compared to monomeric Ir/Re‐lipids. Ir‐liposomes exhibit stronger light absorption and higher emission generation (>threefold) than Re‐liposomes, resulting in superior efficacy against Staphylococcus aureus while maintaining better tolerability toward host cells. Formulations with higher cholesterol (40 mol%) and PEG‐lipid (5%) content demonstrate increased potency against S. aureus. The incorporation of EDTA‐lipid significantly enhances aPDT efficacy but also increases toxicity toward host cells. Incorporation of DOTAP alters the nanoparticles’ surface charge, potentially improving their interaction with bacterial walls, but negatively impacts their stability, leading to aggregation of the nanoparticles. Ir‐HC demonstrates ideal characteristics (effectiveness, selectivity, and stability) for aPDT under the tested conditions, indicating the importance of the structural design of Re‐ and Ir‐complex liposomes for their selectivity in aPDT.
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spelling doaj.art-d224e8bc151440b0826c1730cb7f14472024-02-15T05:52:51ZengWiley-VCHSmall Science2688-40462024-02-0142n/an/a10.1002/smsc.202300131Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic TherapyGiulia Kassab0Neha Manav1Layla Pires2Miffy H. Y. Cheng3Yulin Mo4Hilde H. Buzzá5Iti Gupta6Juan Chen7Gang Zheng8Princess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaDepartment of Medical Biophysics University of Toronto Toronto M5G 1L7 CanadaPrincess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaPrincess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaPrincess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaInstitute of Physics Pontificia Universidad Católica de Chile 7820436 Santiago ChileDepartment of Chemistry Indian Institute of Technology Gandhinagar Gandhinagar 382355 Gujarat IndiaPrincess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaPrincess Margaret Cancer Centre University Health Network Toronto M5G 1L7 CanadaAntimicrobial photodynamic therapy (aPDT) is an alternative to antibiotics that has potential for the treatment of chronic skin wounds, but requires improved, highly selective photosensitizer systems. Rhenium (Re)‐complex‐ and iridium (Ir)‐complex‐based phospholipid conjugates, as PDT‐functional building blocks for liposomes, are presented, and varying structural components and proportion of compounds are explored, including adjusting the cholesterol and polyethylene glycol (PEG)‐lipid contents, incorporating ethylenediaminetetraacetic acid (EDTA)‐lipid, and introducing the cationic lipid 1,2‐dioleoyl‐3‐trimethylammonium propane (DOTAP) to enhance their efficacy and selectivity in aPDT. Ir/Re‐liposomes have nanostructurally enhanced photoactivity compared to monomeric Ir/Re‐lipids. Ir‐liposomes exhibit stronger light absorption and higher emission generation (>threefold) than Re‐liposomes, resulting in superior efficacy against Staphylococcus aureus while maintaining better tolerability toward host cells. Formulations with higher cholesterol (40 mol%) and PEG‐lipid (5%) content demonstrate increased potency against S. aureus. The incorporation of EDTA‐lipid significantly enhances aPDT efficacy but also increases toxicity toward host cells. Incorporation of DOTAP alters the nanoparticles’ surface charge, potentially improving their interaction with bacterial walls, but negatively impacts their stability, leading to aggregation of the nanoparticles. Ir‐HC demonstrates ideal characteristics (effectiveness, selectivity, and stability) for aPDT under the tested conditions, indicating the importance of the structural design of Re‐ and Ir‐complex liposomes for their selectivity in aPDT.https://doi.org/10.1002/smsc.202300131infectionsiridiumliposomesphotodynamic therapyrhenium
spellingShingle Giulia Kassab
Neha Manav
Layla Pires
Miffy H. Y. Cheng
Yulin Mo
Hilde H. Buzzá
Iti Gupta
Juan Chen
Gang Zheng
Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
Small Science
infections
iridium
liposomes
photodynamic therapy
rhenium
title Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
title_full Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
title_fullStr Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
title_full_unstemmed Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
title_short Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy
title_sort structural effect of rhenium and iridium complex liposome composition on their selectivity for antimicrobial photodynamic therapy
topic infections
iridium
liposomes
photodynamic therapy
rhenium
url https://doi.org/10.1002/smsc.202300131
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