Olga Lem, Roosa Kekki, Artturi Koivuniemi, Alexander Efimov, Timo Laaksonen and Nikita Durandin
{"title":"脂质氧化途径在活性氧介导的脂质体货物释放中的作用。","authors":"Olga Lem, Roosa Kekki, Artturi Koivuniemi, Alexander Efimov, Timo Laaksonen and Nikita Durandin","doi":"10.1039/D4MA00535J","DOIUrl":null,"url":null,"abstract":"<p >Reactive oxygen species (ROS)-mediated photooxidation is an efficient method for triggering a drug release from liposomes. In addition to the release of small molecules, it also allows the release of large macromolecules, making it a versatile tool for controlled drug delivery. However, the exact release mechanism of large macromolecules from ROS-sensitive liposomes is still unclear. There are no studies on the effect of lipid oxidation on the release of cargo molecules of different sizes. By using HPLC-HRMS method we analyzed the oxidation products of ROS-sensitive DOTAP lipid in phthalocyanine-loaded DOTAP:Cholesterol:DSPE-PEG liposomes after 630 nm light irradiation of different durations. Shorter illumination time (1–2 minutes) led to the formation of hydroperoxides and vic-alcohols predominantly. Longer 9-minute irradiation resulted already in aldehydes generation. Interestingly, the presence of epoxides/mono-hydroperoxides and vic-alcohols in a lipid bilayer ensured a high 90% release of small hydrophilic cargo molecules <em>i.e.</em> calcein, but not large (≥10 KDa) macromolecules. Oxidation till aldehydes was mandatory to deliver <em>e.g.</em> dextrans of 10–70 kDa with <em>ca.</em> 30% efficiency. Molecular dynamics simulations revealed that the formation of aldehydes is required to form pores or even fully disrupt the lipid membrane, while <em>e.g.</em> presence of hydroperoxides is enough to make the bilayer more permeable just for water and small molecules. This is an important finding that shed a light on the release mechanism of different cargo molecules from ROS-sensitive drug delivery systems.</p>","PeriodicalId":18242,"journal":{"name":"Materials Advances","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491990/pdf/","citationCount":"0","resultStr":"{\"title\":\"The role of lipid oxidation pathway in reactive oxygen species-mediated cargo release from liposomes†\",\"authors\":\"Olga Lem, Roosa Kekki, Artturi Koivuniemi, Alexander Efimov, Timo Laaksonen and Nikita Durandin\",\"doi\":\"10.1039/D4MA00535J\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Reactive oxygen species (ROS)-mediated photooxidation is an efficient method for triggering a drug release from liposomes. In addition to the release of small molecules, it also allows the release of large macromolecules, making it a versatile tool for controlled drug delivery. However, the exact release mechanism of large macromolecules from ROS-sensitive liposomes is still unclear. There are no studies on the effect of lipid oxidation on the release of cargo molecules of different sizes. By using HPLC-HRMS method we analyzed the oxidation products of ROS-sensitive DOTAP lipid in phthalocyanine-loaded DOTAP:Cholesterol:DSPE-PEG liposomes after 630 nm light irradiation of different durations. Shorter illumination time (1–2 minutes) led to the formation of hydroperoxides and vic-alcohols predominantly. Longer 9-minute irradiation resulted already in aldehydes generation. Interestingly, the presence of epoxides/mono-hydroperoxides and vic-alcohols in a lipid bilayer ensured a high 90% release of small hydrophilic cargo molecules <em>i.e.</em> calcein, but not large (≥10 KDa) macromolecules. Oxidation till aldehydes was mandatory to deliver <em>e.g.</em> dextrans of 10–70 kDa with <em>ca.</em> 30% efficiency. Molecular dynamics simulations revealed that the formation of aldehydes is required to form pores or even fully disrupt the lipid membrane, while <em>e.g.</em> presence of hydroperoxides is enough to make the bilayer more permeable just for water and small molecules. This is an important finding that shed a light on the release mechanism of different cargo molecules from ROS-sensitive drug delivery systems.</p>\",\"PeriodicalId\":18242,\"journal\":{\"name\":\"Materials Advances\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491990/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Materials Advances\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/ma/d4ma00535j\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Materials Advances","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/ma/d4ma00535j","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
The role of lipid oxidation pathway in reactive oxygen species-mediated cargo release from liposomes†
Reactive oxygen species (ROS)-mediated photooxidation is an efficient method for triggering a drug release from liposomes. In addition to the release of small molecules, it also allows the release of large macromolecules, making it a versatile tool for controlled drug delivery. However, the exact release mechanism of large macromolecules from ROS-sensitive liposomes is still unclear. There are no studies on the effect of lipid oxidation on the release of cargo molecules of different sizes. By using HPLC-HRMS method we analyzed the oxidation products of ROS-sensitive DOTAP lipid in phthalocyanine-loaded DOTAP:Cholesterol:DSPE-PEG liposomes after 630 nm light irradiation of different durations. Shorter illumination time (1–2 minutes) led to the formation of hydroperoxides and vic-alcohols predominantly. Longer 9-minute irradiation resulted already in aldehydes generation. Interestingly, the presence of epoxides/mono-hydroperoxides and vic-alcohols in a lipid bilayer ensured a high 90% release of small hydrophilic cargo molecules i.e. calcein, but not large (≥10 KDa) macromolecules. Oxidation till aldehydes was mandatory to deliver e.g. dextrans of 10–70 kDa with ca. 30% efficiency. Molecular dynamics simulations revealed that the formation of aldehydes is required to form pores or even fully disrupt the lipid membrane, while e.g. presence of hydroperoxides is enough to make the bilayer more permeable just for water and small molecules. This is an important finding that shed a light on the release mechanism of different cargo molecules from ROS-sensitive drug delivery systems.