Photosensitized Membrane Permeabilization Requires Contact-Dependent Reactions between Photosensitizer and Lipids

Author(s):Show less -

Bacellar, Isabel O. L. ^{[1, 2, 3]} ; Oliyeira, Maria Cecilia ^[4] ; Dantas, Lucas S. ^[1] ; Costa, Elierge B. ^[4] ; Junqueira, Helena C. ^[1] ; Martins, Waleska K. ^[5] ; Durantini, Andres M. ^{[2, 3]} ; Cosa, Gonzalo ^{[2, 3]} ; Di Mascio, Paolo ^[1] ; Wainwright, Mark ^[6] ; Miotto, Ronei ^[4] ; Cordeiro, Rodrigo M. ^[4] ; Miyamoto, Sayuri ^[1] ; Baptista, Mauricio S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

^[2] McGill Univ, Dept Chem, 801 Sherbrook St West, Montreal, PQ H3A 0B8 - Canada

^[3] McGill Univ, Ctr Selfassembled Chem Structures CSACS CRMAA, 801 Sherbrook St West, Montreal, PQ H3A 0B8 - Canada

^[4] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Ave Estados 5001, BR-09210580 Santo Andre, SP - Brazil

^[5] Univ Anhanguera Sao Paulo, Ave Raimundo Pereira Magalhaes 3305, BR-05145200 Sao Paulo, SP - Brazil

^[6] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 3AF, Merseyside - England

• Document type: Journal article
• Source: Journal of the American Chemical Society; v. 140, n. 30, p. 9606-9615, AUG 1 2018.
• Web of Science Citations: 29

Abstract

Although the general mechanisms of lipid oxidation are known, the chemical steps through which photosensitizers and light permeabilize lipid membranes are still poorly understood. Herein we characterized the products of lipid photooxidation and their effects on lipid bilayers, also giving insight into their formation pathways. Our experimental system was designed to allow two phenothiazinium-based photosensitizers (methylene blue, MB, and DO15) to deliver the same amount of singlet oxygen molecules per second to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposome membranes, but with a substantial difference in terms of the extent of direct physical contact with lipid double bonds; that is, DO15 has a 27-times higher colocalization with omega-9 lipid double bonds than MB. Under this condition, DO15 permeabilizes membranes at least 1 order of magnitude more efficiently than MB, a result that was also valid for liposomes made of polyunsaturated lipids. Quantification of reaction products uncovered a mixture of phospholipid hydroperoxides, alcohols, ketones, and aldehydes. Although both photosensitizers allowed the formation of hydroperoxides, the oxidized products that require direct reactions between photosensitizer and lipids were more prevalent in liposomes oxidized by DO15. Membrane permeabilization was always connected with the presence of lipid aldehydes, which cause a substantial decrease in the Gibbs free energy barrier for water permeation. Processes depending on direct contact between photosensitizers and lipids were revealed to be essential for the progress of lipid oxidation and consequently for aldehyde formation, providing a molecular-level explanation of why membrane binding correlates so well with the cell-killing efficiency of photosensitizers. (AU)

• FAPESP's process: 13/11640-0 - Relationship between the photoinduced damage in lipids and membrane permeabilization
• Grantee: Isabel de Oliveira Lima Bacellar
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/22935-7 - Study of photosensitized radical-mediated lipid oxidation by the use of a BODIPY-a-tocopherol off/on fluorescent probe in model membranes
• Grantee: Isabel de Oliveira Lima Bacellar
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/50680-5 - Photosensitization in life sciences
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Projects - Thematic Grants