ArticleInternational journal of nanomedicine2026
Triphenylphosphonium Bolaamphiphile-Liposomes Loaded with Resveratrol and Trolox: Mitochondriotropic Formulations with Therapeutic Potential in Neurodegeneration and Cancer.
Article in International journal of nanomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Novel Azole-Modified Porphyrins for Mitochondria-Targeted Photodynamic Therapy.Molecules (Basel, Switzerland) · 2025Article
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13 authors.
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Abstract
Purpose: We aimed to develop mitochondriotropic liposomes (TPP3-liposomes) formulated with a phospholipid (PC) and the triphenylphosphonium bolaamphiphile TPP3, and encapsulate two antioxidants, trans-resveratrol (hydrophobic) and Trolox (hydrophilic), for mitochondrial therapy of neurodegeneration and drug-resistant tumors. Methods: The influence of the PC (saturated or unsaturated) and TPP3/PC ratio on liposome physico-chemical properties (diameter, polydispersity, charge, transition temperature, and stability over time) were investigated by Dynamic and Dielectrophoretic Light Scattering measurements. Evaluation of cytotoxicity, mitochondrial targeting and effect on mitochondrial membrane potential of TPP3-liposomes were conducted utilizing an MTT assay, laser scanning confocal microscopy and flow cytometry on drug-resistant human breast cancer cells (MDA-MB231) and murine skeletal muscle cells (C2C12): MDA-MB231 cells have been selected as a model for studying multiple drug resistance (MDR) in cancer; C2C12 cells have been chosen to investigate the oxidative stress associated with the ageing process and neurodegenerative muscle diseases. Two different strategies were explored for antioxidant loading: active loading into the liposome aqueous cavity (resveratrol, Trolox) and passive loading inside the lipid bilayer membrane (resveratrol). Results: The amount of TPP3 bolaamphiphile and lipid composition affect liposomes' physicochemical properties, liposome bilayer organization, and antioxidant loading efficiency. TPP3 confers the ability to reach mitochondria even in low amounts (2.5%); liposomes with 2.5% of TPP3 are non-toxic and capable of encapsulating the antioxidants. TPP3-liposomes encapsulating trans-resveratrol in the lipid bilayer membrane or in the aqueous cavity were developed, with high entrapment efficiency in both cases. Trolox was encapsulated in the aqueous cavity of liposomes, without precedents in literature, with very high entrapment efficiency and enhanced stability following encapsulation. TPP3-liposomes can deliver resveratrol to the mitochondria in the MDA-MB231 cells, exerting a protective activity on the mitochondrial structure. Conclusion: Our findings support the potential of antioxidant-loaded liposomes as adjuvants in neurodegenerative diseases or sensitizing agents in cancer therapy.
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